Opioid peptides classes

Schiller PW, Nguyen TM-D, Berezowska I, Weltrowska G, Schmidt R, Marsden BJ, Wilkes BC, Lemieux C, Chung NN. The TIPP opioid peptide family development of a new class of highly potent 6-receptor antagonists with extraordinary -selectivity. In Yanaihara N, ed. Peptide Chemistry 1992 (Proceedings of the 2nd Japanese Symposium on Peptide Chemistry. Leiden, The Netherlands Escom Science Publishers, 1993 337-340. 

A series of peptides, occurring naturally in brain and possessing pharmacological properties similar to those of morphine, have been described. At least three separate families of peptides have opioid properties (Table 24.2), and the different classes of peptides reside in separate distinct neurons. It is likely that the endogenous opioid peptides coexist in neurons with other nonopioid neurotransmitters. The initial hope that these endogenous agents or synthetic derivatives of them would be found to retain the analgesic activity of the opioids but be devoid of respiratory depression and/or addictive properties has now somewhat abated. 

Nyberg, F., Sanderson, K., and Glamsta, E.-L. 1997. The hemorphins a new class of opioid peptides derived from the blood protein hemoglobin. Biopolymers 43, 147-156. 

Dynorphins are a class of endogenous opioid peptides produced by many different populahons of neurons. They function primarily as a K-opioid receptor agonist therefore, they may act as antidote against addiction to cocaine. However, they also have x- and 8-opiod receptor agonist activities. Dynophin A, which is a 17-residue peptide, and Dynophin B, which is a 13-residue pephde, are found in nature. 

Recently, a new class of opioid peptides, the endomorphins (52 and 53, Fig. 7.9), were discovered (264) that do not share the classical "message" sequence with other mammalian opioid peptides. In contrast to other mammalian opioid peptides, the endomorphins show high selectivity for their preferential receptor, the receptor (Table 7.9). Since their discovery the pharmacology of these new mammalian opioid peptides has been studied extensively (see Ref 265 for a detailed review). 

In addition to the four classes of opioid peptides discussed earlier (Section3.4), other peptides of mammalian origin with opioid activity have also been identified. j3-Casomorphin (210), obtained by enzymatic digestion of the milk protein casein (659,660), exhibits some selectivity for jll receptors. Human j3-casomor-phin (211) differs from the bovine sequence in two positions the human /3-casomorphin pen-tapeptide and tetrapeptide fragments are less potent than the corresponding bovine peptides (661). Other peptides with affinity for opioid receptors include peptides derived from hemoglobin (see Ref 662). 

Tire rationale in designing peptides with the substitution of methyl groups at the 2 and 6 position of Tyr (Dint) Dmt-Tic-OH (DTOH) and Dmt-Tic-Ala-OH (DTAOH), was to minimize the message domain of opioid peptides while maintaining activity. Thus, a class of highly potent and selective opioid di- and tripeptide 5 antagonist [72] were synthesized... 

The endogenous opioid peptides are of pharmacological interest because they are highly potent analgesics. The enkephalin class contains small peptides... 

A. Classification and Prototypes Vasoactive peptides comprise a large class of endogenous substances that function as neurotransmitters as well as local and systemic hormones. The better-known peptides include angiotensin, bradykinin, atrial natriuretic peptide, endothelin, vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, vasopressin, glucagon, and several opioid peptides. Vasopressin is discussed in Chapters 15 and 37, the opioid peptides in Chapter 31, and glucagon in Chapter 41. The peptides discussed in this chapter and their effects are summarized in Table 17-1. 

The synthesis and investigation of six novel cycUc enkephalin analogs by Pawlak et al., in which two basic amino acids have been linked by a carbonyl bridge achieved by treatment with bis(4-nitrophenyl)carbonate led to a model of the bioactive conformation of this class of opioid peptides [129]. 

The second application of the CFTI approach described here involves calculations of the free energy differences between conformers of the linear form of the opioid pentapeptide DPDPE in aqueous solution [9, 10]. DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen, where D-Pen is the D isomer of /3,/3-dimethylcysteine) and other opioids are an interesting class of biologically active peptides which exhibit a strong correlation between conformation and affinity and selectivity for different receptors. The cyclic form of DPDPE contains a disulfide bond constraint, and is a highly specific S opioid [llj. Our simulations provide information on the cost of pre-organizing the linear peptide from its stable solution structure to a cyclic-like precursor for disulfide bond formation. Such... 

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