GRF ANALOGS AND FRAGMENTS - CORRELATION BETWEEN RECEPTOR-BINDING, ACTIVITY AND STRUCTURE

被引：52

作者：

CAMPBELL, RM ^{[1
]}

LEE, Y ^{[1
]}

RIVIER, J ^{[1
]}

HEIMER, EP ^{[1
]}

FELIX, AM ^{[1
]}

MOWLES, TF ^{[1
]}

机构：

[1] SALK INST BIOL STUDIES,CLAYTON FDN LABS PEPTIDE BIOL,LA JOLLA,CA 92037

来源：

PEPTIDES | 1991年 / 12卷 / 03期

关键词：

GROWTH HORMONE-RELEASING FACTOR (GRF); GRF ANALOGS; GROWTH HORMONE (GH); RAT ANTERIOR PITUITARY; GRF RECEPTOR BINDING;

D O I：

10.1016/0196-9781(91)90103-V

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

GH-releasing activity in vitro was directly correlated with GRF receptor binding affinity for all hGRF analogs examined. hGRF(1-29)-NH2 analogs with Ala15-substitution (for Gly15) displayed 4-5 times higher affinity for the GRF receptor relative to hGRF(1-44)-NH2. Replacement of Gly15 with Sar15 resulted in a dramatic loss of activity and receptor binding. The present data supports the proposal that Ala15-substitution increases receptor affinity, and hence potency, due to increased amphiphilic alpha-helical interactions. Fragments of hGRF, representative of DPP-IV and trypsin-like cleavage, are inactive as a consequence of greatly diminished GRF receptor binding. These results provide a comprehensive analysis of the structural features required for both GRF receptor binding and activation.

引用

页码：569 / 574

页数：6

共 23 条

[1] BARANY G, 1980, PEPTIDES ANAL SYNTHE, V2, P1
[2] GROWTH-HORMONE RELEASING-FACTOR, SOMATOCRININ, RELEASES PITUITARY GROWTH-HORMONE INVITRO
BRAZEAU, P
LING, N
BOHLEN, P
ESCH, F
YING, SY
GUILLEMIN, R
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (24): : 7909 - 7913
[3] DUBREUIL P, 1990, J ANIM SCI, V68, P1254
[4] FELIX AM, 1988, INT J PEPT PROT RES, V32, P441
[5] FELIX AM, 1988, PEPTIDES CHEM BIOL, P465
[6] FELIX AM, 1987, PEPTIDES 1986, P481
[7] FOURNIER A, 1988, INT J PEPT PROT RES, V31, P86
[8] FRAKER PJ, 1978, BIOCHEM BIOPH RES CO, V80, P849, DOI 10.1016/0006-291X(78)91322-0
[9] DIPEPTIDYLPEPTIDASE-IV AND TRYPSIN-LIKE ENZYMATIC DEGRADATION OF HUMAN GROWTH-HORMONE RELEASING HORMONE IN PLASMA
FROHMAN, LA
DOWNS, TR
HEIMER, EP
FELIX, AM
[J]. JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (05) : 1533 - 1540
[10] RAPID ENZYMATIC DEGRADATION OF GROWTH-HORMONE RELEASING HORMONE BY PLASMA INVITRO AND INVIVO TO A BIOLOGICALLY INACTIVE PRODUCT CLEAVED AT THE NH2 TERMINUS
FROHMAN, LA
DOWNS, TR
WILLIAMS, TC
HEIMER, EP
PAN, YCE
FELIX, AM
[J]. JOURNAL OF CLINICAL INVESTIGATION, 1986, 78 (04) : 906 - 913

← 1 2 3 →