Role of chain termini in selective steroidogenic effect of ACTH/MSH(4-10) on isolated adrenocortical cells.

To investigate the role of charged chain ends in the corticosteroidogenic effect of ACTH/MSH(4-10), acetyl and amide derivatives of ACTH/MSH(4-10) were synthesized and tested in isolated zona glomerulosa and zona fasciculata cells. ACTH/MSH(4-10)-NH2, Ac-ACTH/MSH(4-10) and Ac-ACTH/MSH(4-10)-NH2 (10 microM to 1 mM) stimulated the aldosterone production of zona glomerulosa cells, whereas these peptides did not stimulate the corticosterone production of zona fasciculata cells, even at 1 mM concentration. As ACTH/MSH(4-10) has been shown to have a steroidogenic effect on both types of adrenocortical cells, both charged chain termini seem to be essential for triggering of the corticosterone production of zona fasciculata cells, but for aldosterone production their presence appears not to be important.

TRH analog administration increases endogenous TRH levels in the central nervous system.

Experiments were carried out to increase the endogenous levels of TRH in brain and spinal cord. After 7 days of continuous oral ingestion of TRH analogs (D-pGlu-Leu-ProNH2, pGlu-Leu-Pro, pGlu-Pro-ProNH2, or pGlu-Leu-pyrrolidide), spinal cord and brain levels of TRH were elevated, whereas the content of TRH metabolite, cyclo(His-Pro), was decreased. In addition, the TRH analogs inhibited in vitro metabolism of [3H-Pro]-TRH by brain and spinal cord extracts.

Synthesis of angiotensin II antagonists with variations in position 5.

Six angiotensin II antagonists containing cyclohexylglycine (Chg) or cyclopentylglycine (Cpg) in position 5 were synthesized by stepwise elongation in solution, using the pentafluorophenyl ester method. The influence of substitution on the inhibitory properties of the analogues was studied in four different bioassays. [Sar1,Chg5,Lac8]AII proved to be the most potent antagonist with low intrinsic activity in both the in vitro and in vivo tests.

Solid-phase peptide synthesis using tert.-butyloxycarbonylamino acid pentafluorophenyl esters.

Boc-amino acid pentafluorophenyl esters have been successfully used in solid-phase peptide synthesis. The coupling rates and the purity of the products are comparable to those with the symmetrical anhydrides. These active esters require modified Merrifield resin, polar medium for coupling and in some cases, base catalysis.