New highly specific agonistic peptides for human melanocortin MC(1) receptor.
A peptide with very high specificity for the human melanocortin MC(1) receptor identified by phage display was used as a lead for the design of new peptides. Two new peptides, MS05 and MS09, were synthesized and found to bind with sub-nanomolar affinities to the MC(1) receptor. Both these peptides showed strong agonistic activity at the MC(1) receptor. The MS05 was the most MC(1) receptor selective as it showed virtually no binding affinity for the MC(4) and MC(5) receptors and only micromolar affinity for the MC(3) receptor. The selectivity and potency of the new peptides make them potent tools for studies of MC(1) receptors, as well as novel potential candidate drugs for the treatment of inflammatory conditions.
Szardenings
M
M
Department of Pharmaceutical Pharmacology, Uppsala University, SE-751 24, Uppsala, Sweden.
Muceniece
R
R
Mutule
I
I
Mutulis
F
F
Wikberg
J E
JE
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001667:Binding, Competitive; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000819:agonists* / Q000378:metabolism; D044101:Receptors, Melanocortin
D000893:Anti-Inflammatory Agents; D007457:Iodine Radioisotopes; C408884:MS05 peptide; C408885:MS09 peptide; D010455:Peptides; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor; D000242:Cyclic AMP