Linked Life Data

2882520

Source:http://linkedlifedata.com/resource/pubmed/id/2882520

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1987-5-15
pubmed:abstractText
We synthesized a series of octapeptide analogs of somatostatin, containing N-terminal tryptophan or another amino acid followed by the hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys and a C-terminal threoninamide or tryptophanamide. After purification by HPLC, the inhibitory activities of these analogs on the release of growth hormone (somatotropin) in rats were determined in vivo. The eight octapeptides with an N-terminal tryptophan residue were found to have a greater inhibitory effect than somatostatin. The most potent of these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, was 94.3 times more active than somatostatin. The other analogs, in order of decreasing potency, were Ac-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, D-Trp(For)-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2, Ac-Trp(For)-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, Ac-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2, and D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2. The growth hormone inhibitory activity of these analogs was from 53.7 to 11.6 times greater than that of somatostatin. The octapeptides containing D- or L-tryptophan at the N-terminus, phenylalanine at position 3, and threonine at position 6 exhibited a greater inhibitory effect on growth hormone release than that of the analogs with tyrosine and valine at positions 3 and 6, respectively. Substitution of D-tryptophan for D-phenylalanine at the N-terminus in the octapeptide containing phenylalanine in the third, threonine in the sixth, and threoninamide in the C-terminal position also increased the growth hormone-release inhibitory activity. Time-course assay showed that D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I), in a dose of 1 microgram/kg of body weight, inhibited the release of growth hormone for at least 3 hr. In view of their high activity and prolonged duration of action, some of these analogs could be useful clinically.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2502-6
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Superactive octapeptide somatostatin analogs containing tryptophan at position 1.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't