Abstract |
Corticotropin releasing factor 2 receptor selective analogs of the amphibian peptide sauvagine, a member of the corticotropin releasing factor (CRF) peptide family, have therapeutic potential for the treatment of skeletal muscle atrophy. Previously, we demonstrated that [P11X12X13]Svg peptides have improved CRF2R selectivity, although not to the level of CRF2R selective hormones such as urocortin 2 and urocortin 3. Since we also demonstrated a potential for improvement in selectivity of sauvagine by modifications of residues 35 and 39, we investigated substitutions of these amino acids in selected [P11X12X13]Svg peptides. We have observed that substitution of Arg35 in sauvagine to Ala35 (the amino acid found in all CRF2R selective agonists), increased the selectivity of [P11, X12, X13]Svg analogs. In contrast, substitution of Asp39 in sauvagine to Ala39 (also the amino acid found in all CRF2R selective agonists) did not further increase the selectivity of [P11, X12, X13, A35]Svg analogs. Thus, the residues 35 along with 11, 12, and 13 in sauvagine represent important sites for improving CRF2R selectivity.
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Authors | Adam W Mazur, Feng Wang, Michelle Tscheiner, Elizabeth Donnelly, Robert J Isfort |
Journal | Peptides
(Peptides)
Vol. 26
Issue 5
Pg. 887-91
(May 2005)
ISSN: 0196-9781 [Print] United States |
PMID | 15808919
(Publication Type: Journal Article)
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Chemical References |
- Amphibian Proteins
- CRF receptor type 2
- Peptide Hormones
- Peptides
- Receptors, Corticotropin-Releasing Hormone
- Asparagine
- sauvagine
- Alanine
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Topics |
- Alanine
(genetics)
- Amino Acid Sequence
- Amino Acid Substitution
- Amphibian Proteins
- Animals
- Asparagine
(genetics)
- Binding Sites
- Cells, Cultured
- Humans
- Mice
- Molecular Sequence Data
- Peptide Hormones
- Peptides
(chemistry, genetics, pharmacology)
- Rats
- Receptors, Corticotropin-Releasing Hormone
(agonists)
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