Novel derivatives of gamma-endorphins, intermediates therefor, and compositions and methods employing said derivatives

Novel heptadecapeptides of the formula

• R.sub.1 -Tyr(R.sub.2)-X'-Gly-Phe-Met-Thr(R.sub.3)-Ser(R.sub.3)-Glu(R.sub.4)-Lys(R. sub.5)-Ser(R.sub.3)-Gln-Thr(R.sub.3)Pro-Leu-Val-Thr(R.sub.3)-Leu-Y
• wherein X' is a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-histidine, D-proline, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-aspartic acid, D-asparagine, D-lysine and D-arginine with the limitation that when X' is D-tyrosine, D-threonine, D-serine, D-glutamine, D-lysine, D-aspartic acid or D-arginine, X' is a chiral amino acid residue protected by an R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 protecting group;
• R.sub.1 is a N-terminus solid phase peptide synthesis protecting group selected from the group consisting of acyl-type protecting groups, aromatic urethan-type protecting groups, alkyl-type protecting groups, trialkylsilane groups, or aliphatic urethan protecting groups;
• R.sub.2 is a protecting group for the phenolic hydroxyl group of tyrosine selected from the group consisting of tetrahydropyranol, tert-butyl, trityl, benzyl, 2,4-dichlorobenzyl, benzyloxycarbonyl or 2-bromobenzyloxycarbonyl;
• R.sub.3 is a protecting group for the alcohol hydroxy functions of serine and threonine;
• R.sub.4 is a protecting group for the gamma carboxyl group of glutamic acid;
• R.sub.5 is a protecting group for the epsilon amino group of lysine selected from the group consisting of trifluoracetyl, benzyloxycarbonyl, and 2-chlorobenzyloxycarbonyl;
• and
• R.sub.6 is a protecting group for the quanidine group of arginine;
• Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino, or lower alkoxy and a derivatized insoluble polystyrene resin support represented by the formulae ##STR2##