Structure-activity relationships of a series of [D-Ala2]deltorphin I and II analogues; in vitro blood-brain barrier permeability and stability.

[D-Ala2]deltorphins are enzymatically stable, amphibian heptapeptides that have a higher affinity and selectivity for delta-opioid receptors than any endogenous mammalian compound known. This study investigated the in vitro blood-brain barrier permeability, using primary bovine brain microvessel endothelium culture, and the resistance to enzymatic degradation, in mouse 15% brain membrane homogenates and 100% plasma, of [D-Ala2]deltorphin I, [D-Ala2]deltorphin II and several analogues. Derivatives were designed with the addition of N-terminal neutral and basic amino acids or with alterations of the amino acids present within the deltorphin sequences.

Comparison of GH-stimulation by GH-RH(1-29)NH2 and an agmatine29 GH-RH analog, after intravenous, subcutaneous and intranasal administration and after pulmonary inhalation in rats.

Many studies have shown that human GH-RH(1-29)NH2 possesses full intrinsic activity of GH-RH(1-44)NH2 in vitro and in vivo. This investigation was performed to evaluate the efficacy of GH-RH(1-29)NH2 given by different routes of administration in stimulating GH release in rats. In each case GH-RH(1-29)NH2 was administered intravenously, subcutaneously, intranasally and by pulmonary inhalation at two different doses to groups of seven males rats.

Development of a radioimmunoassay for some agonists of growth hormone-releasing hormone.

A radioimmunoassay (RIA) method was developed for determination of superactive GH-RH agonist Dat1,Ala15,Nle27 GH-RH(1-28)Agm29 (MZ-2-51) and some of the related analogs in biological fluids. The analogs were radioiodinated using the Bolton-Hunter method. For the generation of antibodies, rabbits were immunized with MZ-2-51 and its C-terminal derivative Nle27 GH-RH(17-28)Agm29, conjugated to bovine serum albumin with glutaraldehyde.

Potent agonists of growth hormone-releasing hormone. II.

Analogs of the 29-amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) or Lys-NH2 in position 29 have been synthesized by the solid-phase method, purified, and tested in vitro. Except for one peptide, all analogs contained desaminotyrosine (Dat) in position 1. All contained Nle27 in order to avoid oxidation of Met27.

Potent agonists of growth hormone-releasing hormone. Part I.

Analogs of the 29 amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) in position 29 have been synthesized by the solid phase method, purified, and tested in vitro and in vivo. The majority of the analogs contained desaminotyrosine (Dat) in position 1, but a few of them had Tyr1, or N-MeTyr1. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27, and/or 28.