Long-acting peptide analogs
View Patent ↗Long-acting agonistic analogs for CLR/RAMP receptors are provided that have an extended half-live in vivo.
1. A biologically active adrenomedullin peptide conjugate has the structure:
wherein said peptide consisting of SEQ ID NO: 6 and R 1 is a linear or branched C 3 -C 100 alkyl optionally substituted with halo, hydroxy, alkoxy, amino, alkylamino, dialkylamino, sulfate, or phosphate, and which may by saturated, or mono- or di-unsaturated; and
the conjugate having a serum half-life of greater than 1.5 hours with the alkyl moiety conjugated to the amino terminus of said SEQ ID NO: 6.
2. The peptide of claim 1 , wherein R 1 is selected from palmitate; stearate; arachidic acid; lauric acid; myristic acid; myristoleic acid; palmitoleic acid; sapienic acid; oleic acid; linoleic acid; α-linolenic acid; arachidonic acid; eicosapentaenoic acid; erucic acid; and docosahexaenoic acid.
3. A pharmaceutical composition comprising a therapeutically effective dose of the peptide of claim 1 , and a pharmaceutically acceptable excipient.
4. A biologically active human adrenomedullin peptide that consists of the amino acid sequence set forth as SEQ ID NO:6, modified by conjugation of palmitate to the amino terminus of the peptide, wherein the modified peptide has a serum half-life of greater than 1.5 hours.