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GROWTH-HORMONE SECRETAGOGUES - CHARACTERIZATION, EFFICACY, AND MINIMAL BIOACTIVE CONFORMATION
被引：67
作者：
MCDOWELL, RS
ELIAS, KA
STANLEY, MS
BURDICK, DJ
BURNIER, JP
CHAN, KS
FAIRBROTHER, WJ
HAMMONDS, RG
INGLE, GS
JACOBSEN, NE
MORTENSEN, DL
RAWSON, TE
WON, WB
CLARK, RG
SOMERS, TC
机构：
[1] GENENTECH INC,DEPT ENDOCRINE RES,S SAN FRANCISCO,CA 94080
[2] GENENTECH INC,DEPT PROT CHEM,S SAN FRANCISCO,CA 94080
[3] GENENTECH INC,DEPT PROT ENGN,S SAN FRANCISCO,CA 94080
来源：
关键词：
D O I：
10.1073/pnas.92.24.11165
中图分类号：
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号：
07 ;
0710 ;
09 ;
摘要：
Another class of growth hormone (GH) secretagogues has been discovered by altering the backbone structure of a flexible linear GH-releasing peptide (GHRP). In vitro and in vivo characterization confirms these GH secretagogues as the most potent and smallest (M(r) < 500) reported. Anabolic efficacy is demonstrated in rodents with intermittent delivery. A convergent model of the bioactive conformation of GHRPs is developed and is supported by the NMR structure of a highly potent cyclic analog of GHRP-2. The model and functional data provide a logical framework for the further design of low-molecular weight secretagogues and illustrate the utility of an interdisciplinary approach to elucidating potential bound-state conformations of flexible peptide ligands.
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页码：11165 / 11169
页数：5
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