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Interferons Part A PDF

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Contributors to Volume 78 Article numbers are in parentheses following the names of contributors. Affiliations listed are current. mann Medical College, Philadelphia, JOHN A. GNORTSMRA (55), Department of Pennsylvania 20191 Microbiology, Graduate School of Public HSALIAK C. CHADnA (31, 80), Department Health, University of Pittsburgh, Pitts- of Cell and Tumor Biology, Roswell Park burgh, Pennsylvania 16251 Memorial Institute, Buffalo, New York LEUMAS NORAB (l, 49, 50, 60), Department 36241 of Microbiology, The University of Texas ARINUOM K. CHELBI:ALIX (82), lnstitut de Medical Branch, Galveston, Texas 05577 Biologie PhysicoChimique , ER 832 CNRS-u. 542 INSERM, 75005 Paris. KURT BERG (70), Institute of Medical Mi- France crobiology, Bartholin Building, Univer- sity of Aarhus, DK-8000 Aarhus C., Den- NERUAL OLLETSOC (11), Roche Institute of mark Molecular Biology, Nutley, New .lersey 01170 ALFONS BILL1AU (13, 65), Rega Institute, G. COUPIN (23), Laboratoire ed Virologie et Faculty of Medicine, University of Leu- Microbiologie G~ndrale, UER des Sci- ven, B-3000 Leuven, Belgium ences Pharmaceutiques, Universit~ Louis DRAHREG ODOB (9), Ernst-Boehringer-lnsti- Pasteur, 84076 Strasbourg Cedex, France tur for Arzneimittelforschung, .rD ERli¢ DE QCREEC (32, 40), Department o/ Boehringer-Gasse 5-11, A-II21 Vienna, Human Biology, Division of Microbio- Austria logy, Rega Institute for Medical Re- ERNEST BOLLIN, JR. (24), Photo Products search, Katholieke Universiteit Leuven. Department, E. I. ud Pont de Nemours 0003-B Leuven, Belgium and Company, Inc., Wilmington, Dela- ENIEEUQAJ DE DRANGIUG-REYEAM (73), ware 89891 Institut Curie-Biologie, Campus d'Orsay, Batiment 110, ,51 Rue Georges Clemen- YRAM C. BREINIG (16), Department of Mi- crobiology, Graduate School of Public ceau, 50419 Orsay, France Health, University of Pittsburgh, Pitts- ODNANIDREF DIANZANI (21, 51, 60), De- burgh, Pennsylvania 16251 partment of Microbiology, The University of Turin, Turin, Italy R. BROEZE (18), Department of Molecular Biophysics and Biochemistry, Yale Uni- LoIs B. EPSTEIN (19, 20), Cancer Research versity. New Haven, Connecticut 11560 Institute, and Department of Pediatrics, University of California, San Francisco, YRAG R. BURLESON (35), Department of Microbiology, University of Notre Dame, California 34149 South Bend, Indiana 65564 OTSENRE FALCOFF (78), Institut Curie, F. E. LLEBPMAC (42), Laboratory of Chemi- Section ed Biologie, 13257 Paris Cedex ,50 cal Biology, National Institute of France Arthritis, Diabetes, and Digestive and PHILIP C. FAMILLETTI (5, 6, ,11 43, 56), -eD Kidney Diseases, National Institutes of partment of Molecular Genetics. Hoff- Health, Bethesda, Maryland 50202 mann-La Roche Inc., Nutley, New Jersey KARl CANTELL (4, 41, 71), Central Public 01170 Health Laboratory, SF-00280 Helsinki ,82 B. REINNOCUAF (23), Laboratoire ed Bac- Finland t(riologie et Virologie, UER ed M(de- WILUAM A. CARTER (7, 81), Clinical Re- cine et de Pharmacie, Universit( ed search and Oncology, Orlowitz Institute Rennes, 35043 Rennes Cedex, France for Cancer and Blood Diseases, Hahne- NAMRON B. F1NTER (2, 57), Virology Re- xiii xiv CONTRIBUTORS TO VOLUME 87 search and Development Department, biology. Bartholin Building, University of Wellcome Research Laboratories, Lang- Aarhus, DK-8000 Aarhus C., Denmark ley Court, Beckenham, Kent BR3 3BS, TREBOR D. GRERHSREH (6), Process Devel- England opment, Genentech Incorporated, South HEINZ-JORGEN FR1ESEN (63), Research San Francisco, California 08049 Laboratories of Behringwerke AG, D- SINIKKA HIRVONEN (4, 41, 71), Central 3550 Marburg/Lahn, Federal Republic of "cilbuP Health Laboratory, SF-00280 Hel- Germany sinki ,82 Finland J. FUJISAWA (74), Institute for Virus Re- OTNOM HO (16), Department of Microbi- search, Kyoto University, Kyoto, 606, ology, Graduate School of Public Health, Japan and Division of lnfectious Diseases, De- ANGEL S. VOBALAG (28), Department of -iV partment of Medicine, School of Medi- rology, Institute of Infectious and Para- cine, University of Pittsburgh, Pitts- sitic Diseases, Medical Academy, Sofia- burgh, Pennsylvania 16251 ,7251 Bulgaria ANNOD S. SHBOH (68, 72), Department of YZREJ A. SEDAIGROEG (21, 75, 77), Immuno Biochemistry, Roche Institute of Molecu- Modulators Laboratories, Ltd., Stafford, lar Biology, Nutley, New Jersey 01170 Texas 77477 JULIUS S. ZCIWEZSOROH (12), Department EGROEG E. GIFFORD (27), Immunology and of Biological Resources, Roswell Park Medical Microbiology, University of -rolF Memorial Institute, Buffalo, New York adi College of Medicine, Gainesville, 36241 Florida 01623 OKIHASAM IIZUKA (59), Basic Research DIVAD J. NOR1G (58), Department of Micro- Laboratories, Toray Industries, Inc., biology and Immunology, Wright State ,1 111, Tebiro, Kamakura, 842 Japan University, School of Medicine, Dayton, D. ILLINGER (23), Laboratoire de Virologie Ohio 53454 et Microbiologie ,elarOndG UER des Sci- HSEKAR M. AHROOG (44), Division of -loriV ences Pharmaceutiques, Universit~ Louis ogy, St. Jude Children's Research Hospi- Pasteur, 84076 Strasbourg Cedex, France tal, Memphis, Tennessee 10183 Y. aRUZ~AWI (74), Institute for Virus Re- PETER M. GROB (80), Department of Bio- search, Kyoto University~ Kyoto 606, chemical Sciences, Princeton University, Japan Princeton, New Jersey 44580 AlCIRTAP NOSEMAJ (35, 36, 45, 52, 83), De- SIDNEY g. GREBSSORG (35, 36, 39, 45, 52, partment of Microbiology, ehT Medical 53, 83), Department of Microbiology, The College of Wisconsin, Milwaukee, Wis- Medical College of Wisconsin, Milwau- consin 62235 kee, Wisconsin 62235 B. JAYAgAM (18), Department of Molecular EILEEN G. ARO1CSUG (6), Central Research Biophysics and Biochemistry, Yale Uni- Division, Hoffman-La Roche Inc., Nut- versity, New Haven, Connecticut 11560 Icy, New Jersey 01170 KCIREDERF H. JOHNSON,JR.(7), HEM Re- SALOHCIN HAHON (54), Public Health Ser- search, Rockville, Maryland 25802 vice, Appalachian Laboratory for Occu- DRAWOH M. NOSNHOJ (21, 75, 77), Depart- pational Safety and Health, and Depart- ment of Microbiology, The University of ment of Pediatrics, West Virginia Texas Medical Branch, Galveston, Texas University School of Medicine, Morgan- 05577 town, West Virginia 50562 LEAHCIM D. NOTSNHOJ (57), Wellcome Re- K. J. W. HEINE (65), Abbott Laboratories, search Laboratories, Langley Court, North Chicago, Illinois 46006 Beckenham, Kent BR3 3BS, England REVI NOREH (70), Institute of Medical Micro- GNAGFLOW K. JOKLIK (79), Department of CONTRIBUTORS TO VOLUME 78 XV Microbiology and Immunology, Duke NERRAW P. LEVY (68), Unigene Laborator- University Medical Center, Durham, ies, Inc., Nutley, New Jersey 01170 North Carolina 01772 LEO S. LIN (69), Cetus Corporation, Berke- ATREBOR M. KAMIN (20), Department of ley, California 01749 Neurology, University of California, San JEAN LINDENMANN (25), Institute for Im- Francisco, California 34149 munology and Virology, University ~f HANNA-LEENA KAUPP1NEN (4), Finnish Zurich, POB, CH-8028 Zurich, Switzer- Red Cross Blood Transfusion Service, land 0130O-FS Helsinki ,13 Finland R. E. LLOYD (50), Department of Micro- Y. KAWADE (17, 74), Institute for Virus biology, ehT University of Texas Medical Research, Kyoto University, Kyoto 606, Branch, Galveston, Texas 05577 Japan NOBUTOSm MAEHARA (37), The Kitasato LORAC KENNY (64), Lovelace Medical Cen- Institute, Tokyo 108, Japan ter, Albuquerque, New Mexico 80178 HPESOJ F. METZGER (48), Pathology Divi- KCIREDERF KLEIN (10), National Cancer sion, United States Army Medical Re- Institute, Frederick Cancer Research search Institute of Infectious Diseases, Center, Frederick, Maryland 10712 Fort Detrick, Frederick, Maryland 10712 TSENRE KNIGHT, JR. (61), Central Research TREBOR S. MILLER (5), New York Blood and Development Department, E. I. ud Center, New York, New York 12001 Pont ed Nemours and Company, Inc., MOLAHSVA MIZRAHI (8, 29), Department of Wilmington, Delaware 89891 Biotechnology, Israel Institute for Biolog- USAYEGIS IHSAYABOK (59), Basic Research ical Research. Ness Ziona .05407 Israel Laboratories, Toray Industries, Inc., JOAN M. MOEHRING (26), Department of .1 111, Tebiro, Kamakura, 842 Japan Medical Microbiology, The University of VESA KOISTINEN (71), Finnish Red Cross Vermont, College of Medicine, Burling- Blood Transfusion Service, 0130O-FS Hel- tolt, Vermont 50450 sinki ,13 Finland PAGE S. NAHAROM (35), Medical College of LEAHCIM J. KRAMER (39), Department of Virginia, ehT Virginia Commonwealth lmmunotherapy Hoffmann-La Roche University, Richmond, Virginia 91232 Inc., Nutley, New Jersey 01170 NHOJ A. AREHCSOM (64, 68), The Biopolymer HSIANG-FU KUNG (72), Department of Mo- Department, Central Research Division, lecular Genetics, Hoffmann-La Roche Hoffmann-La Roche Inc., Nutlev New Inc., Nutley, New Jersey 01170 Jersey 170 I0 NVERAM P. DROEGNAL (49, 50, 51), Depart- LEE W. MOZES (15), Papanicolaou Cancer ment of Microbiology, The University of Research Institute, Miami, Florida 10133 Texas Medical Branch, Galveston, Texas GUNNAR MYLLYL'~ (4), Finnish Red Cross 05577 Blood Transfusion Service, 0130O-FS Hel- P. LEVGNEL (18), Department of Molecular sinki ,13 Finland Biophysics and Biochemistry, Yale Uni- YASUITt NAGANO (37), National Sagami- versity, New Haven, Connecticut 11560 hura Hospital. Sagamihara 228, Japan NASUS S. LEONG (12), Department of Bio- logical Resources, Roswell Park Memo- JUDITH A. O'MALEEY (29, 76), Department of Laboratory Medicine, Medical Virol- rial Institute, Buffalo, New York 36241 ogy Section, Roswell Park Memorial In- NOTLIH B. LEVY (34), National Institute of stitute, Buffalo, New York 36241 Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland MARK A. I-ICSNALEAP (46), Biophysics Lab- 50202 oratoo, of the Graduate School, and -eD xvi CONTRIBUTORS TO VOLUME 78 partment of Biochemistry, University of LIHEOEHT STAEHELIN (72), Pharma Re- Wisconsin-Madison, Madison, Wisconsin search Division, Hoffmann-La Roche and 60735 Company, Ltd., CH-4002 Basel, Switzer- YENDIS AKTSEP (1, 3, 5, 6, ,11 56, 63, 67, 68, land 72), Department of Biochemistry, Roche G. JOHN NOTNATS (49, 50, 51), Department Institute of Molecular Biology, Nutley, of Microbiology, ehT University of Texas New Jersey 01170 Medical Branch, Galveston, Texas 05577 ALUAP M. PITHA (33), The Johns Hopkins YELNATS STEIN (63, 64), Roche Institute of Oncology Center, Biochemical Virology Molecular Biology, Nutley, New Jersey Laboratory, Baltimore, Maryland 50212 01170 P. NORDNIOP (23), Laboratoire de Virologie WILLIAM E. STEWART II (69), Interferon Laboratories, Memorial Sloan-Kettering et Microbiologie Gdndrale, UER des Sci- Cancer Center, New York, New York ences Pharmaceutiques, Universit~ Louis 12001 Pasteur, 84076 Strasbourg Cedex, France NERRAW R. STINEBRING (26), Department TREBOR T. STTEKCIR (10), National Cancer of Medical Microbiology, The University Institute, Frederick Cancer Research of Vermont, College of Medicine, Bur- Center, Frederick, Maryland 10712 lington, Vermont 50450 AIHTNYC A. ROSE (6, 11), Department of DALE A. WOLLEFGNIRTS (38), Cancer and Molecular Genetics, Hoffmann-La Roche Virus Research, The Upjohn Company, Inc., Nutley, New Jersey 01170 Kalamazoo, Michigan 10094 MEHCANEM RUBINSTEIN (67), The Weiz- OR1J SUZUKI (59), Basic Research Labora- mann Institute of Science, Rehovot, Is- tories, Toray Industries, Inc., ,1 111, -eT lear biro, Kamakura, 842 Japan ARAS NIETSNIBUR (5, 6, 56), Department of H. TAmA (18), Department of Pure and Ap- Biochemistry, Roche Institute of Molecu- plied Science, University of Tokyo, 1-8-3 lar Biology, Nutley, New Jersey 01170 Komaba, Jeguro-ku, Tokyo ,351 Japan DNALOR R. RUECKERT (46), Biophysics Y. H. NAT (14, 62), Division of Medical Bio- Laboratory of the Graduate School, and chemistry, Faculty of Medicine, Univer- Department of Biochemistry, University sity of Calgary, Calgary, Alberta T2N of Wisconsin-Madison, Madison. Wiscon- 4NI, Canada nis 60735 YRREJ L. ROLYAT (39), Department of -iM J. JAMES SEDMAK (53, 83), Department of crobiology, The Medical College of -siW Microbiology, ehT Medical College of consin, Milwaukee, Wisconsin 62235 Wisconsin, Milwaukee, Wisconsin 62235 M. N. THANG (82), Institut de Biologie, E. YRETTALS (18), Department of Biologi- PhysicoChimique, ER 832 CNRS - U 542 cal Chemistry, Washington University INSERM, 50057 Puris, France School of Medicine, St. Louis, Missouri PAUL F. ECNERROT (40, 47), National Insti- 01136 tute of Arthritis, Diabetes, Digestive, and DLAREG DLEFNENNOS (22), Department of Kidney Diseases, National Institutes of Microbiology and Immunology, Univer- Health, Bethesda, Maryland 50202 sity of Louisville School of Medicine, J. NAV EMMAD (13), Rega Institute, Faculty Louisville, Kentucky 29204 of Medicine, University of Leaven, B- 0003 Leuven, Belgium DRANOEL SPERO (48), Pathology Division, United States Army Medical Research JAN VILCEK (15, 30), Department of Micro- Institute of Infectious Diseases, Fort biology, New York University Medical Detrick, Frederick, Maryland 10712 Center, New York, New York 61001 CONTRIBUTORS TO VOLUME 78 xvii ALAN A. NAMDLAW (5), Greater New York S. ARAHENOY (74), Tokyo Metropolitan In- Blood Program, New York Blood Center, stitute of Medical Science, Bunkyo-kn, New York, New York 12001 Tokyo 113, Japan D. A. TNEGI~IW (49, 50), Department of Mi- PETER A. YOUNG (57), Wellcome Research crobiology, The University of Texas Med- Laboratories. Langley ('oart. Beckeu- ical Branch, Galveston, Texas 77550 ham, Kent BR3 3BS, England JUANA WIETZF.RBIN (78), lnstitut Curie. TREBOR E. ZIEGLER (79), Department ~f Section de Biologie, 75231 Paris Cedex 05, Medicine, Barnes Hospital, St. Louis. France Missouri 63110 Y. OTOMAMAY (17, 74), Institute Jot Virus KaTHRVN C. ZOON (42, 66), Bureau of Bio- Research, Kyoto University, Kyoto 606, logics, Division of Biochemistry and Bio- Japan physics, Federal Drug Administration, Y. K. YP (30), Department of Microbiol- Bethesda. Maryland 20205 ogy, New York University Medical Cen- ter, New York, New York 10016 Preface Progress in interferon research, as in other areas, has reflected ad- vances in the development of new biological and chemical technologies. The methods described in Volumes 78 and 79 of "Interferons" reflect these achievements. By the early 1970s, basic studies on interferon induc- tion allowed the production of small amounts of interferon so that studies on its purification could begin. Of the three classes of interferon (fibro- blast, leukocyte, and immune), fibroblast and leukocyte interferons were the focus of attention in many laboratories. The methods for purifying these interferons are described in Volume 78. With the development of sensitive methods for the assay of amino acids and peptides, the application of high-performance liquid chromatog- raphy (HPLC) to protein purification was convenient and feasible, partic- ularly with substances that were available in minute amounts. The purifi- cation of interferon by reverse and normal phase HPLC was the first achievement of the purification of proteins by these high-performance procedures. Since then, numerous other proteins have been purified by HPLC with the use of these same techniques. As has been illustrated by additional examples, achievements in interferon research, as in this case, initiated the foundations for achievements in other areas. Even though some of the interferons were purified, only small amounts were available. However, it was possible to determine their amino acid composition, peptide maps, and some of their amino acid se- quences even with picomole to nanomole (0.2 to 02 ~g) amounts. The sec- tions in Volume 79 describe these methods. After the development of assays that could detect the synthesis of bio- logically active interferons in cell-free extracts and by microinjection directly into intact cells from isolated mRNA, it was feasible to consider cloning the DNA coding for these molecules. The methods leading to and including the construction and identification of DNA recombinants con- taining the interferon-coding sequences are described in Volume 79. As a result of the rapid application of these techniques, the complete amino acid sequences of human fibroblast and several leukocyte interfer- ons are now known (see Figs. 1 and 2). Both of these have been expressed in bacteria. Recombinant leukocyte interferon has been purified to homo- geneity and has been in clinical trial for about seven months. The isolation of monoclonal antibodies to leukocyte interferon was instrumental in the effective purification of recombinant human leukocyte interferon as well as in the development of convenient immunoassays for the detection of leukocyte interferon. Crystals of recombinant interferon have been ob- tained and will enable the elucidation of their tertiary structure by X-ray XX PREFACE 5' 1S $I0 02S 12S mec chr ash tys cys ueZ ueZ ~tn ire ala leu leu leu cys phe 8er Chr chr ala leu set TEM gE$ t~ NSA GTA CCA CAA GAA TGT CTC CTC AAC TTA CG CTC GTC GTT CGT CTT CCT T~A ACA TCG TTC CCT GTA CGA CAT CAA 50 01 02 LEO LKU GLY PHE LEU GLN ARG SER SER ASN PH~ CLN CYS GLN LYS LEU LEU TRP GLN LEU ASN GLY ARG LgU ~s~GLU GTT TTC AGG CTT ATC AAC AGA CGA CG~ TAA TTT CA6 TGr CAG AAG CTC CT6 TGG CAA TTG AAT GGG AGG CTT OOl o3 40 50 TYR GYS LEU LYS PSA ARG MET ASN PHE ASP ILE PRO GLU GLU ILE LYS GLN LEU GLN GLN PHK GIN LYS GLU ASP TAT CGT CTC 6AA CAG GGA GTA CAA TTr CAG CTA rCC GAG GAG TTA GAA 6AC GTC GAC GAC CTT GAC GAA GAG CAG 002 60 07 ALA ALA LEU THR ILE TYR GLU MET LEU GLN ASN ILE PHE ALA ILE PHE A~G GLN ASP $EK SEK SEg Trig GLY TRP CCG ACG GTT CCA CTA FAT GAG GTA CT5 GAC CAA CTA TTT TCG TTA CTT AGA AAC TAG ACr TCT CGA TCA CGG ~ST 052 3oo 80 90 i00 ASN GLU tHE ILK VAL GLU ASN LEO LEU ALA ASN VAL TYR HIS GLN ILK ASN HIS LEU L~$ THK VAL LEU GLU GLU TAA GAG TCA TTA Gr GAG CAA CTC GTC TCG TAA CTG TAT TAC GAC ATA CAA TAC 6TC GAA ACA crG cr6 AAG AAG 053 ll0 o21 LYS LEU GLD LYS GLU ASF PHE THR ARG GLY LYS LEU MET SE~ SER LKU HIS LEU LYS ARG TYK TYK GLY ARG ILE AAA CrG GAG AAA GAA GAT TrT ACC A~G GGA AAA CTC GTA CGA TGA GTC CAC GTC AAA AGA TAT TAT GGG GGA ATI 400 054 031 140 150 ~U HIS ~YR UEL LYS ALA LYS GLU TYR SER HIS CYS ALA TRP TflR ILE VAL ARG VAL GLU ILE LKU ARG ASN PHE GTC TAC CAT GTC GAA CCG GAA GAG CAT TGA CAC IGT CCG GGT CCA ATA C!G AGA GT6 AAG CTA ATC GGA CAA TTT 005 061 I66 TYR File ILE ASN AI~G UED THR GLY TYR LEO ARG ASN END CAT CTT TTA CAA AGA TTC ACA TGG CA! CFC ACGA AACGTCTCGITAACAG GCATACAGGGTCTCC CAGGTTCCGATCCCTAGA o55 600 TTGAGTAIrAAATATTrTrAAAGTTTAGA~GATCACAGGAAAGTAAACGTCAFGTAA~CG~TAGTCAGTGAATTTGTC~TA~A~ACCMCrTCrT 650 700 AAAACGTGGTT~TTArTAAATAAAAGGTTTFATTTTAAATTTA~TTATTTTTA 057 3' FIG. 1. DNA and amino acid sequence corresponding to recombinant human leukocyte interferon A (IFLrA). See Volume 79 for references. crystallography. Despite these achievements, much needs to be learned about the biological activity, mode of action, and the clinical efficacy of the interferons. The availability of sufficient amounts for these studies will undoubtedly lead to new insights during this next phase of interferon research. Very much needs to be learned about the "old" interferons, and we will certainly have some additional new ones in the future. The methods in these volumes cover the gamut of these paths. The contributors to these volumes have spent much time and effort in preparing detailed reports of their methodologies. I am grateful to them all for their many excellent contributions. The staff of Academic Press has been most efficient and supportive throughout this undertaking. Drs. Colowick and Kaplan have provided much sound advice since the time these volumes were initiated. Many colleagues and associates have given me numerous useful suggestions. Special thanks are owed to Sophie Cuber who, with accustomed dedication and thoroughness, provided es- PREFACE xxi AAT CGT AAA GAA GGA CAT CTC ATA TAA ATA GGC CAT ACC CAT GGA GAA AGG ACA TTC TAA CTG CAA CCT -I00 Sl Met Thr Asn Lys TTC GAA GCC TTT GCT CTG GCA CAA CAG GTA GTA GGC GAC ACT GTT CGT GTT GTC AAC~T-~ACC AAC AAG 1 Cys Leu Leu Gln Ile Ala Leu Leu Leu Cys Phe Phe Thr Thr Ala Leu Ser Met Set Tyr ASh Leu Leu TGT CTC CTC CAA ATT GCT CTC CTG TTG TGC TTC TTC ACT ACA GCT CTT TCC ~T-~AGC TAC AAC TTG CTT Gly Phe Leu Gln Arg Set Set Ash Phe Gln Cys Gln Lys Leu Leu Trp Gin Leu ASh Gly Arg Leu Glu GGA TTC CTA CAA AGA AGC AGC AAT TTT CAG TGT CAG AAG CTC CTG TGG CAA TTG AAT GGG AGG CTT GAA I00 Tyr Cys Leu Lys Asp Azg Met ASh Phe Asp Ile Pro GIu GIu Ile Lys Gin Leu Gln Gln Phe Gln Lys TAC TGC CTC AAG GAC AGG ATG AAC TTT GAC ATC CCT GAG GAG ATT AAG CAG CTG CAG CAG TTC CAG AAG 200 Glu Asp Ala Ala Leu Thr lie Tyr Glu Met Leu Gln ASh Ile Phe Ala Ile Phe Arg Gln Asp Set Set GAG GAC GCC GCA TTG ACC ATC TAT GAG ATG CTC CAG AAC ATC TTT GCT ATT TTC AGA CAA GAT TCA TCT Set Thr Gly Trp ASh Glu Thr lle Val Glu ASh Leu Leu Ala ASh Val Tyr His Gln lle Ash His Leu AGC ACT GGC TGG AAT GAG ACT ATT GTT GAG AAC CTC CTG GCT AAT GTO TAT CAT CAG ATA AAC CAT CTG 300 Lys Thr Val Leu GIu Glu Lys Leu Glu Lys Glu Asp Phe Thr Arg Gly Lys Lqu Met Ser Ser Leu His AAG ACA GTC CTG GAA GAA AAA CTG GAG AAA GAA GAT TTC ACC AGG GGA AAA CTC ATG AGC AGT CTG CAC 400 Leu Lys Arg Tyr Tyr Gly Arg Ile Leu His Tyr Leu Lys Ala Lys Glu Tyr Ser His Cys Ala Trp Thr CTG AAA AGA TAT TAT GGG AGG ATT CTG CAT TAC CTG AAG GCC AAG GAG TAC AGT CAC TGT GCC TGG ACC 166 Ile Val Arg Val GIu Ile Leu Arg Ash Phe Tyr Phe Ile ASh Arg Leu Thr Gly Tyr Leu Arg Ash END ATA GTC AGA GTG GAA ATC CTA AGG AAC TTT TAC TTC ATT AAC AGA CTT ACA GGT TAC CTC CGA AAC 500 AGA TCT CCT AGC CTG TGC CTC TGG GAC TGG ACA ATT GCT TCA AGC ATT CTT CAA CCA GCA GAT GCT GTT 600 TAA GTG ACT GAT GGC TAA TGT ACT GCA TAT GAA AGG ACA CTA GAA GAT TTT G~ ATT TTT ATT AAA TTA 700 TGA GTT ATT TTT ATT TAT TTA AAT TTT ATT TTG GAA AAT AAA TTA TTT TTG GTG CAA AAG TCA ACA TGG CAG TTT TAA TTT CGA TTT GAT TTA TAT AAC CAT CCA TAT TAT AA 800 FIG. 2. DNA and amino acid sequence corresponding to human fibroblast interferon as deduced from the DNA sequence of the gene. See Volume 79 for references. sential editorial assistance; and to Robert Pestka, for his skill and con- scientiousness in preparing the comprehensive Subject Index for this vol- ume. During the preparation of these volumes, my family has accepted and borne many of my responsibilities in good spirit. Joan has continually sustained an atmosphere for this and other work to be accomplished. Robert, Sharon, and Steven have provided many joys and much good humor vital to me. SIDNEY PESTKA METHODS IN ENZYMOLOGY EDITORS-IN-CHIEF yendiS P. Colowick Nathan O. Kaplan EMULOV VIII. Complex Carbohydrates Edited by ELIZABETH F. NEUFELD DNA ROTCIV GRUBSNIG EMULOV IX. Carbohydrate Metabolism Edited by WILLIS A. DOOW EMULOV X. Oxidation and Phosphorylation Edited by DLANOR W. KOORBATSE DNA DRANYAM E. NAMLLUP EMULOV XI. Enzyme Structure Edited by C. H. W. HIRS EMULOV XII. Nucleic Acids (Parts A and B) Edited by ECNERWAL NAMSSORG DNA KIVIE EVADLOM EMULOV XIII. Citric Acid Cycle Edited by J. M. NIETSNEWOL EMULOV XIV. Lipids Edited by J. M. NIETSNEWOL EMULOV XV. Steroids and Terpenoids Edited by DNOMYAR B. NOTYALC EMULOV XVI. Fast Reactions Edited by KENNETH NITSUK EMULOV XVII. Metabolism of Amino Acids and Amines (Parts A and B) Edited by TREBREH ROBAT DNA CELIA WHITE ROBAT EMULOV XVIII. Vitamins and Coenzymes (Parts A, B, and C) Edited by DLANOD B. KCIMROCCM DNA LEMUEL D. THGIRW XXV xxvi METHODS IN ENZYMOLOGY EMULOV XIX. Proteolytic Enzymes Edited by GERTRUDE E. PERLMANN DNA LASZLO LORAND EMULOV XX. Nucleic Acids and Protein Synthesis (Part )C Edited by KIVIE MOLDAVE DNA LAWRENCE NAMSSORG EMULOV XXI. Nucleic Acids (Part )D Edited by LAWRENCE NAMSSORG DNA KIVlE EVADLOM EMULOV XXII. Enzyme Purification and Related Techniques Edited yb WILLIAM B. YBOKAJ EMULOV XXIII. Photosynthesis (Part A) Edited by ANTHONY NAS PIETRO EMULOV XXIV. Photosynthesis and Nitrogen Fixation (Part B) Edited by ANTHONY NAS PIETRO EMULOV XXV. Enzyme Structure (Part B) Edited by C. H. W. HIRS DNA SERGE N. TIMASHEFF EMULOV XXVI. Enzyme Structure (Part C) Edited by C. H. W. HIRS DNA SERGE N. TIMASHEFF VOLUME XXVII. Enzyme Structure (Part D) Edited yb C. H. W. HIRS DNA SERGE N. FFEHSAM1T EMULOV XXVIII. Complex Carbohydrates (Part B) Edited by VICTOR GRUBSNIG EMULOV XXIX. Nucleic Acids and Protein Synthesis (Part E) Edited by LAWRENCE NAMSSORG DNA KIVIE EVADLOM VOLUME XXX. Nucleic Acids and Protein Synthesis (Part F) Edited by KIVlE MOLDAVE DNA LAWRENCE NAMSSORG EMULOV XXXI. Biomembranes (Part A) Edited by SIDNEY FLEISCHER DNA LESTER REKCAP EMULOV XXXII. Biomembranes (Part B) Edited by SIDNEY FLEISCHER DNA LESTER REKCAP

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