Cholecystokinin synthesis

We have already discussed the co-occurrence of small amine and peptide neurotransmitters their release is normally Ca + dependent, and they operate through signal transmission. They are also capable of regulating each other s release and even the synthesis, clustering, and affinity of receptors. Neuroendocrine cells are capable of producing more than one peptide, and thus an amine-peptide as well as a peptide-peptide combination is possible. It is known, for instance, that the vagus nerve contains substance P, vasointestinal peptide, enkephalin, cholecystokinin, and somatostatin— peptides with a hybrid combination of neural and hormonal communication properties. 

Kurano Y, Kimura T, Sakakibara S. Total synthesis of porcine cholecystokinin-33 (CCK-33). J. Chem. Soc. Chem. Commun. 1987 323-325. 

Penke B, Zarandi M, Zsigo J, Toth GK, Kovacs K, Telegdy G. Synthesis of cholecystokinin peptides. Pept. Proc. Eur. Pept. Symp., 19th. 1987 447-450. 

Penke B, Nyerges L. Solid-phase synthesis of porcine cholecystokinin-33 in a new resin via Emoc strategy. Peptide Res. 1991 4 289-295. 

Boden, P.R. et al. (1993) Cholecystokinin dipeptoid antagonists Dest, synthesis, and anxiolytic profile of some novel CCKA and CCKB selective aird mixed CCKA/CCKB antagonists. / Med. Chem.. 36. 552-565. 

Amine (S)-(+)-97 is needed for the synthesis of a gastrointestinal hormone antagonist, Merck s cholecystokinin antagonist 96, by acylation with indole-2-carboxylic acid. 

Meng, L.P., Joshi, R., and Eckstein, H. (2006) Application of enzymes for the synthesis of the Cholecystokinin Pentapepticle (CCK-5). A contribution to green chemistry. Chim. Oggi-Chem. Today, 24 (3), 50-53. 

G. Ratcliffe, Targeted molecular diversity, design and development of non-peptide antagonists for cholecystokinin and tachykinin receptors, Immunopharmacology 1996, 33, 68-72 D.C. Horwell, W. Howson, G.S. Ratcliffe, H.M.G. Willems, The design of dipeptide helical mimetics the synthesis, tachykinin receptor affinity and conformational analysis of... 

Some genes which show late expression after addition of CDF/LIF have been identified. For example, in cultured sympathetic neurons CDF/LIF induces transcription of not only the acetylcholine gene, but also the genes coding for substance P, somatostatin, cholecystokinin, enkephalin and vasoactive intestinal polypeptide (Nawa and Patterson, 1990 Fann and Patterson, 1994). The transcription of muscarinic acetylcholine receptor genes and substance P receptor genes is also induced (Ludlam et al., 1994). On the other hand, CDF/LIF suppresses catecholamine synthesis. In osteoblast-like cells, LIF suppresses alkaline... 

Calcitonin is secreted continuously under conditions of normocalcemia, and the synthesis of calcitonin is increased when the calcium concentrations in plasma and intracellular fluids increase. Hypermagnesemia has a similar effect on calcitonin production. In hypocalcemia, the production of calcitonin falls. The gastrointestinal hormones—gastrin, glucagon, cholecystokinin, and secretin—and high dietary calcium also stimulate calcitonin production. Long-term hypercalcemia may cause hyperplasia of the C cells. 

Alternatively, the [[9-][(9-fluorenylmethyloxycarbonyl)amino]xanthen-3-yl]oxy]acetic acid linker (Fig. 22, 62) has been applied successfully to the synthesis of the 0-sulfate-tyrosine cholecystokinin octapeptide (residues 26-33) [206], In this case, the cleavage-deprotection was carried out in a single step using TFA-DCM-H2O (1 18 1) for 15 min at 45°C. The overall yield was 71% and the target peptide represented >95% of the total crude material. The acid-labile PAL-linked resin 9 [203,204] and the 4-succinylamino-2,2, 4 -trimethoxyben-zhydrylamine (SAMBHA) linker (Fig. 22, 63) [205] have also been used in this approach. Sodium salt formation increased the acid stability of the O- and S-sulfate groups. Therefore, the peptide resin is preferentially washed with 1 M aqueous NaBr/DMF (1 2 v/v) [207] or a methanolic NaOH solution before the cleavage [205]. 

Phthalimidomethyl-substituted 477-pyrido[4,3-( ]-l-thia-2,4-diazine 1,1-dioxide derivative 125 undergoes hydrazino-lysis to produce the (7-3-aminomethyl-substituted product, which is then acylated to yield the amido adducts 126 (R = H, Ph R =Ar, NHAr) as potential cholecystokinin/gastric receptor ligands (Equation 17) <1997BSB781>. Similar acylation chemistry has been applied to the synthesis of related 5-(methylamides) of 2/7-benzo-l-thia-2,4-diazine 1,1-dioxides (see Section 9.05.9.1.3) <2001CHE237>. 

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