Development of specific and non-specific somatostatin analogs.
Biological activity of six somatostatin analogs has been investigated. In these analogs, disulfide bond is replaced by ethylene bond cyclized with alpha-amino suberic acid. In addition, they contain unique D-configuration in both Trp8 and Cys14 moiety with dicarba substitution. An analog of the short chain length, C omega 7-cyclo (Phe6-Phe7-D-Trp8-Lys9-Thr10-Phe11-D-Asu14) (analog 4) has suppressive effect for GH, but not for other hormones. Analog 6, C omega 9-cyclo(Asn5-Phe6-Phe7-D-Trp8-Lys9-Thr10-Ph e11-Thr12-D-Asu14), has suppressed GH and insulin secretion, but not for gastrin and glucagon. Analog 1, C omega 11-cyclo (Lys4-Asn5-Phe6-Phe7-D-Trp8-Lys9-Thr10-Phe11- Thr12-Ser13-D-Asu14] and 5, C omega 9-cyclo (Lys4-Asn5-Phe6-Phe7-D-Trp8-Lys9-Thr10-Phe11-D-+ ++Asu14) have broad suppressive effect for GH, gastrin, insulin and glucagon release after arginine infusion. The shortest analog, analog 2, C omega 5-cyclo (Phe7-D-Trp8-Lys9-Thr10-D-Asu14) has weak suppressive effect of GH, insulin and glucagon secretion, and it is suggested that Phe6 and Phe11 are necessary for the appearance of suppressive effect of GH. Specific analog, analog 4, may be useful for the future treatment for acromegaly and diabetic retinopathy. Nonspecific analogs, 1 and 5 are candidates for the clinical application of wide variety.
Nakano
T
T
Harano
Y
Y
Emura
J
J
Kimura
T
T
Sakakibara
S
S
Shigeta
Y
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000097:blood; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D001786:Blood Glucose; D005755:Gastrins; D007328:Insulin; D013004:Somatostatin; D013006:Growth Hormone; D005934:Glucagon; D001120:Arginine