A collection of nature-inspired design of domain-specific peptides
This library is being continuously updated to include all new and current peptides including GnRH(1-5) (GPR101 and GPR173), SDF-1-alpha (CXCR4 receptor), Ela-32 and Ela-21 (APJ), SCNH2/Apelin-prepropeptide(42-57), TLQP-21 (C3a or C1q receptor), D-[Lys3]GHRP-6 (CCR5), Neuronostatin (GPR107), Pepcan-12 (CB1) Fractalkine peptides, cysteine-modified or C-terminally truncated INSLs and truncated GLP-1Peptide 34 (GPR54), Fertilization promoting peptide (TCP11), Head Activator Neuropeptide (GPR37), Obestatin( GPR39), Neuromedin S, Neuropeptide S, QRFP-43, PBAN, P518, NPB & NPW, INSL 3 & 7, Endokinin A/B, AF9, BK), receptors (FM-4/TGR-1, NPSR, GPR100, GPR135, GPR142, GPR103, GPR7 & 8, LGR7 & 8, CG6986, NPR-1, PBAN-R) and references.
It has been suggested that several different active conformations of the receptor may exist dependent on the properties of the agonist. Therefore, properly selection with modified peptide ligands for a biased signalling properties may allow the development of drugs that selectively modulate only the therapeutically relevant physiological functions, thereby decreasing the risk of side effects.
Three sub-families in “Class A GPCRs” contains being recognized when comparing their amino-acid sequences. Receptors to different families share no sequence similarity. Group 1a contains GPCRs for small ligands and the receptors of the retinal/odorants/opiates/enkephalins. Group 1b contains receptors for peptides whose binding site includees the N-terminal, the the extracellular loops and superior parts of transmembranes. Group 1c contains GPCRs for glycoprotein hormones. “Class B GPCRs” have a similar morphology to group 1c but they do not share any sequence homology. Additional Class includes the family of pheromone receptors(VNs0 and family of “frizzled” and “smoothened (Smo) receptors which involved in embryonic development. Finally, the cAMP receptors (cAR) have only seen found in D. discoideum but its possible expression in vertebrate has not yet been reported.
Figure and part of texts: “The EMBO Journal (1999) 18, 1723–1729”.
This gPeptide Library (L-004) contains more than 1000 peptides. Each of the peptide has a specific property to interact at least with a known subclass of GPCRs
A schematic representation of how the two-state receptor model relates to the action of drugs as strong agonists, partial agonists, neutral competitive antagonists, inverse agonists, and inverse partial agonists. The inactive and active receptor conformations (R and R*, respectively) are in constant equilibrium.
Figure: Raymond C. Stevens et al., GPCR Network: a large-scale collaboration on GPCR structure and function. Nat Rev Drug Discov. 2013 January; 12(1): 25–34.
Social Network Confirmation