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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1985-3-20
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pubmed:abstractText |
In previous reports illustrating the effects of conformational restriction of the N-terminal region of human pancreatic growth hormone releasing factor, we demonstrated that D-amino acid substitutions in either of positions 1, 2, or 3 resulted in greatly increased growth hormone releasing activity both in vivo and in vitro. The most active compound, [D-Ala-2]GRF(1-29)NH2, was 51 times more active than the parent 29 amino acid peptide in the sodium pentobarbital anesthetized rat. These observations have now been extended to analogues containing multiple D-amino acid replacements in these three positions. Once again, peptides with superagonist potencies ranging from 1200% to 3800% were obtained after solid-phase synthesis and purification by medium-pressure reverse-phase liquid chromatography. In addition, it was found that [D-Asn-8]- and [D-Ala-4]GRF(1-29)NH2 were, respectively, 2.43 and 1.1 times more active than GRF(1-29)NH2 itself. In contrast, [D-Phe-6] and [D-Thr-7] analogues were virtually inactive. Chou-Fasman structural predictions suggest that the first three residues of the peptide assume no fixed type of conformation but that a reverse turn could be present between residues 6 and 10. Attempts are made to rationalize the biological results with these calculations. The effects of other side chains on the D-amino acid in position 2 were also investigated. Both the Ac-[D-Phe-2]- and Ac-[D-Arg-2]peptides had very low activity. Several of the inactive peptides were tested as possible antagonists of GRF; however, none was able to block the stimulatory effects of GRF(1-29)NH2 after combined administration.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
181-5
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:3918170-Amino Acid Sequence,
pubmed-meshheading:3918170-Amino Acids,
pubmed-meshheading:3918170-Animals,
pubmed-meshheading:3918170-Cells, Cultured,
pubmed-meshheading:3918170-Chromatography, High Pressure Liquid,
pubmed-meshheading:3918170-Growth Hormone-Releasing Hormone,
pubmed-meshheading:3918170-Hydrolysis,
pubmed-meshheading:3918170-Male,
pubmed-meshheading:3918170-Peptide Fragments,
pubmed-meshheading:3918170-Pituitary Gland,
pubmed-meshheading:3918170-Protein Conformation,
pubmed-meshheading:3918170-Rats
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pubmed:year |
1985
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pubmed:articleTitle |
Structure-activity studies on the N-terminal region of growth hormone releasing factor.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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