Enkephalin analogues

Enkalon Enkastat Enkatherm Enkephalin analogues Enkephalinase Enkephalinase A Enkephalins... 

V2. Vermes, I., Szontagh, L and Telegdy, G., In vitro effects of a synthetic enkephalin analogue (d-Met2, Pro5)-enkephalinamide on the hypothalamus-pituitary-testis function in rats. Neurosci. Lett. 11,201-204(1979). 

Scheme 13 Solid-Phase Peptide Synthesis of an Enkephalin Analogue by Macrocyclization of Cysteine and Dehydroalaninel271...

B pMeBHA (HF) enkephalin analogues dynorphin analogues Fmoc Boc/OtBu Bzl [106361379.380]... 

Pless, J., Bauer, W., Cardinaux, F., Closse, A., Hauser, D., Hugenin, R., Roemer, D., Buescher, H.-H., Hill, R.C. Synthesis, opiate receptor binding and analgesic activity of enkephalin analogues, Helv. Chim. Acta 1979, 62, 398-411. 

Roemer D., Buescher H. H., Hill R. C., Pless J., Bauer W., Cardinaux F., Closse A., Hauser D., Huguenin R., A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity, Nature 1977, 268, 547-549... 

The Z-alkene isostere mimics the cis-amide bond conformation. Its molecular volume and log p values are almost identical to those of the E-isostere (Table 1). Its use in bioactive peptides is very limited, probably because of the synthetic challenge involved. One study reports the migration of the double bond to the a,(3-position in an enkephalin analogue. 4 The Z-alkene in the Alat t[Z, CH=CH]Pro dipeptide isostere, however, was reported to be stable towards isomerization.1 1X1 orf/to-Substituted aromatic or tetrazole rings have been used more frequently as ds-amide bond mimics. 

Scheme 55 Oxazabicyclic p-Turn Peptidomimetic and the Enkephalin Analogue Containing the Peptido-mimetid174 ...

Huffman et alJ161 have also incorporated a /ram-alkene y-turn mimetic into a series of enkephalin analogues 14 (Scheme 9) with complete loss of biological activity and into an HIV-1 protease inhibitor replacing the -Asn-Tyr-Pro- sequence in 15 corresponding to the P2-Pi-P( positions of the peptide substrate giving 16[39-401 (Scheme 10). 

Incorporation of a-Saal by solution-phase synthesis, used to demonstrate its influence on the conformation of a linear peptide, has been performed for the Leu-enkephalin analogue H-Tyr-a-Saal-Phe-Leu-OMe (59) in which the Saa replaces the Gly-Gly dipeptide segment of the natural sequence H-Tyr-Gly-Gly-Phe-Leu-OH (Scheme 9).[45 ... 

Uchiyama, T., Kotani, A., Tasumi, H., et al. Development of novel lipophilic derivatives of DADLE (leucine enkephalin analogue) Intestinal permeability characteristics of DADLE derivatives in rats. Pharm. Res. 17 1461-1467, 2000. 

K. Prokai-Tatrai, L. Prokai, and N. Bodor, Brain-targeted delivery of a leucine-enkephalin analogue by retrometabolic design, J. Med. Chem. 39 4775 (1996). 

Apart from these specific bindings, peptides and proteins may also be non-spe-cifically bound to plasma proteins. For example, metkephamid, a met-enkephalin analogue, was described as being 44—49% bound to albumin [64], while octreotide, a somatostatin analogue, is up to 65% bound to lipoproteins [27]. 

Polt, R., Porreca, F., Szabo, L Z., et al. (1994). Glycopeptide enkephalin analogues produce analgesia in mice evidence for penetration of the blood-brain barrier. Proc. Natl. Acad. Sci. USA 91, 7114-7118. 

STABLE ENKEPHALIN ANALOGUES [D-Ala2, D-Leu5] ENKEPHALIN (DADLE) AND [D-Ala2, N-Me-Phe4, Met(0)5-ol]ENKEPHALIN (FK 33-824) ARE SELECTIVE DELTA AND MU AGONISTS, RESPECTIVELY... 

An examination of the structure-activity relationship (SAR) of a series of enkephalin analogues and morphine derivatives in competing with the binding of radioisotope labeled DADLE and FK 33-824 or opiates revealed that DADLE binds to an opioid receptor selective to Leu-enkephalin and its analogues. In contrast, FK 33-824, morphine, or naloxone binds to opioid receptors with selectivity in favor of morphine and derivatives simi-... 

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