Nonapeptides

DETAILED DESCRIPTION OF THE INVENTION In accordance with this invention there is provided a novel group of nonapeptides of formula I: ##STR1## in which the A groups are hydrogen or a direct bond between the two sulfur atoms; X is hydrogen or NH.
sub.
2 ; X.
sub.
1 is L-Trp or D-Trp; X.
sub.
2 is L-Abu, L-Val, L-Phe or L-Thr; and the two cysteinyl moieties are of L- or D- configuration, the linear precursor intermediates or pharmaceuticaly acceptable salts thereof.
In the depicted formula and throughout this specification and claims, where the chirality of an amino acid is not indicated or otherwise stated, it is understood to be of the L-series.
The linear precursor intermediates, which comprise an additional aspect of the invention may be depicted as follows in formula II: ##STR2## in which R is hydrogen or a protected .
alpha.
-amino group; R.
sup.
1 is a sulfhydryl protecting group; R.
sup.
2 is an amino protecting group; X.
sub.
1 is L-Trp or D-Trp; X.
sub.
2 is L-Abu, L-Val, L-Phe, or L-Thr; R.
sup.
3 is a sulfhydryl protecting group; and the two cysteinyl moieties are of L- or D- configuration.
These intermediates comprise the fully protected nonapeptide bound to a hydroxymethylated polystyrene resin support employed in solid phase synthesis of the polypeptide.
The pharmaceutically acceptable salts of the compounds (I) of this invention are those non-toxic addition salts produced by known methods from acids conventionally employed with pharmaceuticals such as hydrochloric, hydrobromic, sulfuric, phosphoric, polyphosphoric, maleic, acetic, citric, benzoic, succinic, malonic or ascorbic acid and the like.
Acetic acid is the preferred acid.
The nonapeptides I selectively inhibit release of glucagon without materially altering blood levels of growth hormone or insulin.
As such, they are useful in treatment of hyperglycemia in general and specifically in diabetes mellitus which is characterized by excessive glucagon secretion and deficient insulin release.
Thus, for example, the postprandial hyperglycemic state in insulin-dependent diabetes may be improved through suppression of excessive glucagon by administration of the compounds of this invention with or without concomitant administration of suboptimal amounts of exogenous insulin