RECEPTOR (SSTR4)- SELECTIVE SOMATOSTATIN ANALOGS

摘要

Analogs of SRIF which are selective for SSTR4 in contrast to the other cloned SRIF receptors are useful in determining tissue and cellular expression of the receptor SSTR4 and its biological role in regulating tumor growth. SRIF analog peptides, such as des-AA^{1,2,4,5,12,13} [Ala⁷] -SRIF; des­-AA^{1,2,4,5,12,13} [Aph⁷] -SRIF, des-AA^{1'2,4,5,12,13} [Aph⁷] Cbm-SRIF; des­AA^1,4,5,12,13 [Tyr² Ala⁷] -Cbm-SRIF, and des-AA^{1'2,4,5,12,13} [Tyr⁷, C^BMe-L­2Nal⁸]-SRIF, and counterparts incorporating D-Cys³ and/or D­Trp⁸ and/or Ala¹¹, bind with high affinity to the cloned human receptor SSTR4 and activate the receptor, but they do not bind with significant affinity to human SSTR1, SSTR2, SSTR3 or SSTR5. By incorporating an iodinated tyrosine in position-2 in these SSTR4-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, cytotoxins or highly radioactive elements can be N-terminally coupled or complexed thereto.