TY - JOUR
T1 - A backbone-cyclic, receptor 5-selective somatostatin analogue
T2 - Synthesis, bioactivity, and nuclear magnetic resonance conformational analysis
AU - Gilon, Chaim
AU - Huenges, Martin
AU - Matha, Barbara
AU - Gellerman, Gary
AU - Hornik, Vered
AU - Afargan, Michel
AU - Amitay, Oved
AU - Ziv, Ofer
AU - Feller, Etty
AU - Gamliel, Asher
AU - Shohat, Dvira
AU - Wanger, Mazal
AU - Arad, Oded
AU - Kessler, Horst
PY - 1998/3/12
Y1 - 1998/3/12
N2 - Cyclo(PheN2-Tyr-D-Trp-Lys-Val-PheC3)-Thr-NH2 (PTR 3046), a backbone- cyclic somatostatin analogue, was synthesized by solid-phase methodology. The binding characteristics of PTR 3046 to the different somatostatin receptors, expressed in CHO cells, indicate high selectivity to the SSTR5 receptor. PTR 3046 is highly stable against enzymatic degradation as determined in vitro by incubation with rat renal homogenate and human serum. The biological activity of PTR 3046 in vivo was determined in rats. PTR 3046 inhibits bombesin- and caerulein-induced amylase and lipase release from the pancreas without inhibiting growth hormone or glucagon release. The major conformation of PTR 3046 in CD3OH, as determined by NMR, is defined by a type II' β-turn at D- Trp-Lys and a cis amide bond at Val-PheC3.
AB - Cyclo(PheN2-Tyr-D-Trp-Lys-Val-PheC3)-Thr-NH2 (PTR 3046), a backbone- cyclic somatostatin analogue, was synthesized by solid-phase methodology. The binding characteristics of PTR 3046 to the different somatostatin receptors, expressed in CHO cells, indicate high selectivity to the SSTR5 receptor. PTR 3046 is highly stable against enzymatic degradation as determined in vitro by incubation with rat renal homogenate and human serum. The biological activity of PTR 3046 in vivo was determined in rats. PTR 3046 inhibits bombesin- and caerulein-induced amylase and lipase release from the pancreas without inhibiting growth hormone or glucagon release. The major conformation of PTR 3046 in CD3OH, as determined by NMR, is defined by a type II' β-turn at D- Trp-Lys and a cis amide bond at Val-PheC3.
UR - http://www.scopus.com/inward/record.url?scp=15644375594&partnerID=8YFLogxK
U2 - 10.1021/jm970633x
DO - 10.1021/jm970633x
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C2 - 9526566
AN - SCOPUS:15644375594
SN - 0022-2623
VL - 41
SP - 919
EP - 929
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 6
ER -