From our continuing studies on the synthesis and conformation of the luteinizing hormone-releasing hormone (LH-RH) analogs, the following conclusions can be made: 1. The in vitro agonist activity of the three newly synthesized analogs of LH-RH ranges from 0.0001% through 0.006% to 2-3%. 2. The nmr studies of the 15N analogs suggest that there are two possible conformers for the (D-Ala6) LH-RH analog: a C7 ring or a Beta-turn involving the amino acid residues 4-7. This conformational flexibility may explain the enhanced biological activity of this analog. We are also carrying out the synthesis of a retro-inverso modified Ala5-somatostatin analog. This modification makes all three postulated cleavage sites fall within the modifid region while leaving intact the part essential for biological activity of this hormone. The biological activity and metabolism of this analog will be studied.
| Mierke, D F; Lucietto, P; Goodman, M et al. (1987) Conformational studies of diastereomeric cyclic enkephalins by 1H-NMR and computer simulations. Biopolymers 26:1573-86 |
| Richman, S J; Goodman, M; Nguyen, T M et al. (1985) Synthesis and biological activity of linear and cyclic enkephalins modified at the Gly3-Phe4 amide bond. Int J Pept Protein Res 25:648-62 |
| Pallai, P V; Struthers, R S; Goodman, M et al. (1985) Partial retro-inverso analogues of somatostatin: pairwise modifications at residues 7 and 8 and at residues 8 and 9. Biochemistry 24:1933-41 |
| Goodman, M (1985) Peptide homologs, isosteres, and isomers: a general approach to structure-activity relationships. Biopolymers 24:137-55 |
