Insulin
It is fourteen years since insulin was last reviewed in The Handbook of Ex perimental Pharmacology, in volume 32. The present endeavor is more modest in scope. Volume 32 appeared in two separate parts, each having its own subeditors, and together the two
- PDF / 91,276,218 Bytes
- 481 Pages / 481.89 x 685.98 pts Page_size
- 29 Downloads / 193 Views
Experimental Pharmacology Volume 92 Editorial Board G.v. R. Born, London
P. Cuatrecasas, Ann Arbor, MI
H. Herken, Berlin
Insulin Contributors 1 Avruch' 11 Bahl ' 0. Brandenburg . R.Bressler P. Cuatrecasas . U Derewenda . Z.S. Derewenda . G. G. Dodson We. Duckworth· I.D Goldfine' lR. Gunsalus . M.D. Hollenberg R.E. Hubbard' S. Jacobs ' C.R. Kahn· T. Kono . 1M. Kyriakis 1 Lamer' lR. Levy · R.A. Liddle' WI Malaisse' lL. Messina 1M. Olefsky . 0.1 Price ' R.A. Roth , P. Rothenberg R.l Rushakoff· A.R. Saltiel' D.E Steiner' H.S. Tager H.E. Tornqvist· M.D Walker ' M.E White' lA. Williams E.l Yurkow ' K. Zierler
Editors
P. Cuatrecasas and S. Jacobs
Springer-Verlag Berlin Heidelberg New York London Paris Tokyo HongKong
Professor PEDRO CUATRECASAS, M. D. President, Pharmaceutical Research Division Warner Lambert Company, 2800 Plymouth Road Ann Arbor, MI 48105, USA STEVEN JACOBS, M. D. Director, Division of Cell Biology Burroughs Wellcome Co. Research Triangle Park, NC 27709, USA
With 86 Figures ISBN-13: 978-3-642-74100-5 DOl: 10.1007/978-3-642-74098-5
e-ISBN-13: 978-3-642-74098-5
Library of Congress Cataloging-in-Publication Data. Insulin/editors, Pedro Cuatrecasas and Steven Jacobs; contributors, J. Avruch ... let al.]. p. cm. - (Handbook of experimental pharmacology; v. 92) (U.S.) 1. Insulin-Physiological effect. I. Cuatrecasas, P. II. Jacobs, Steven, 1946-. III. Avruch, J. IV. Series. QP905.H3 vol. 92 [QP572.I5j615'1 s- H
A
I
~
C\
Insulin Chemistry
7
very useful for the isolation and characterization of insulin receptors (FINN et al. 1984 a, b; HOFMANN et al. 1984, 1987). The potential of the acid-labile citraconyl group (for citraconylinsulins, see NAITHANI and GATTNER 1982; ZAITSU et al. 1985) has not yet been fully explored. Single-chain intermediates (MARKUSSEN et al. 1987 a) obviate protection at A1. r1.Amino groups have also been protected in COOH terminal semisyntheses (see below). NH2 terminal shortening by Edman degradation and semisynthesis requires temporary protection with acid-stable groups, such as the Msc and, most recently, the Fmoc moiety (INOUYE et al. 1985). Thus, CAO et al. (1986) have e1ongated>bis-Msc-des(Bl-B4)insulin with Boc-Gly-Pro-Glu(OBut) to give an insulinjIGF-I hybrid, and have replaced B5-histidine by alanine via sequential coupling of two peptides to bis-Msc-des(B1-B5)-insulin. Semisynthesis at the A chain is more complicated and typically requires the following steps: 1. TemporaryprotectionatA1 (Boc) 2. Protection at B1 and B29 (Msc) 3. Deblocking at A1 4. Edman degradation of glycine (and further cycles, if desired) 5. Substitution at'the amino group 6. Deprotection Following this protocol, TRINDLER and BRANDENBURG (1982) replaced Gly by several different residues, and DAVIES and OFFORD (1985) by [3H]Gly. Somewhat different strategies were followed for the semi synthesis of L- or D-Trp Al-insulins (GEIGER et al. 1982), and [A1,B1 Ala] insulin (SAUNDERS and FREUDE 1982), as well as [Ala A3]insulin (INOUYE et al. 1985).
II. Hydroxy Amino Acids Sulfated insulins exhibit
