Endomorphin-2 derivatives

Endomorphin derivatives with improved pharmacological properties 13CMD2741. 

Perhaps most importantly, MOP agonists can potentiate HIV propagation in lymphocytes, monocytes, and monocyte-derived macrophages/microglia (Peterson et al. 1990 Carr and Serou 1995). This includes morphine (Peterson et al. 1990, 1999, 2004 Hu et al. 2005), methadone (Douglas 2001), and the MOP peptide agonist endomorphin (Peterson et al. 1999). The effects of morphine on HIV... 

Subsequently, numerous peptides with opioid-like effects have been found in the central nervous system and in peripheral tissues. These endogenous opioid peptides vary in size, but their amino terminals mostly share a similar enkephalin sequence of amino acids. Currently, four separate, individually gene-derived families of endogenous opioid peptides are recognized the endorphins, the enkephalins, the dynorphins and the endomorphins [17a], -Endorphin interacts predominantly with n and 6 receptors, Leu-enkephalin and Met-enkephalin interact predominantly with 5 receptors, dynorphin shows preference for k receptors [17b], while endomorphins 1 and 2 exhibit... 

Labuz D, Berger S, Mousa SA, ZoUner C, Rittner HL, Shaqura MA, Segovia-SUvestre T, Przewlocka B, Stein C, Machelska H (2006) Peripheral antinociceptive effects of exogenous and immune cell-derived endomorphins in prolonged inflammatory pain. J Neurosci 26 4350-4358... 

The endogenous ligands for the opioid receptors are peptides known as the endorphins (endogenous morphine) or opio-peptins. These include the pentapep tides methionine-enkephalin and leucine-enkephalin and a hep tapep tide and octapeptide version of methionine-enkephalin, all derived from preproenkephalin p-endorphin derived from proopiomelanocortin a-and p-dynorphin derived from prodynorphin endomorphin-1 and -2, whose precursor has not been definitively identified and orphanin FQ or nociceptin, derived from OFQ/N precursor protein. These peptides are discussed in more detail in Chapter 34. 

Like morphiceptin and PL017, cisltrans isomerization occurs around the Tyr-Pro amide bond in endomorphin-1, with similar populations (75%trans, 25%cis) found for the two conformations (819). Based on structural comparison of the cis and trans conformations of endomorphin-1 to other /x- and 8-selective opioid peptides, Podlogar et al. proposed that the trans conformation was the bioactive form (819). Recently, Schiller and coworkers reported endomorphin-2 and morphiceptin analogs containing a pseudoproline derivative in... 

Macrocyclic modulators of the p-opioid reeeptor inelude cyclic p-casomor-phin- and enkephalin- analogs as well as so ealled atypical cyclic peptides derived from endomorphin-1. 

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