Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using appropriate amino acid active esters (3 eq.) in presence of HOBt (1 eq.) and employing DPM protection for the thiol function of cysteine, a rapid synthesis of oxytocin in the solid phase has been accomplished. The DPM group has been removed by sodium-liquid ammonia reduction since boiling TFA is ineffective. Desaminooxytocin and 4-Thr-oxytocin have been synthesized using lesser quantities of amino acid active esters (1.5 eq.) in presence of HOBt (1 eq.), but the durations of coupling are longer. The solid-phase synthesis of desamino-oxytocin using appropriate Boc-amino acids in presence of DCCI in toluene medium has been described. Toluene does not exert any significant accelerating influence on the coupling rate as it does when active esters are employed.
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PMID:Solid-phase synthesis of oxytocin, desaminooxytocin and 4-Thr-oxytocin using active esters in presence of 1-hydroxybenzotriazole. 70 Sep 21

Disulfide-containing peptides may be obtained in good yields and purities when oxidations are carried out on peptide chains anchored to polymeric supports used for solid-phase synthesis. Such approaches take advantage of the pseudo-dilution phenomenon which favors intramolecular processes. A variety of procedures have been demonstrated using the related model peptides Ac-Cys-Pro-D Val-Cys-NH2 and Ac-Pen-Pro-D Val-Cys-NH2 (which both readily assume a type II beta-turn conformation that becomes stabilized by a 14-membered disulfide-containing intramolecular ring), and oxytocin (conformationally mobile 20-membered disulfide ring). Both Boc and Fmoc were used for N alpha-amino protection, the beta-thiols of cysteine or penicillamine were blocked by S-acetamidomethyl (Acm), S-9-fluorenylmethyl (Fm), or S-trityl (Trt), and compatible anchoring linkages included HF-labile 4-methylbenzhydrylamide (MBHA), TFA-labile tris (alkoxy)benzylamide (PAL), and photolabile o-nitrobenzylamide (Nonb). Assemblies of linear sequences proceeded smoothly, and polymer-supported oxidations were carried out in a variety of ways either directly or after deblocking to the resin-bound dithiol. Chains were released from the support without substantial damage to the disulfide bridges, and overall yields were as high as 60-90%.
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PMID:Cyclization of disulfide-containing peptides in solid-phase synthesis. 191 96

Treatment of a mixture of Cys(R)(O) and Cys(R') with an acid was found to generate cystine in fairly good yields, when suitable R, R', and an acid were selected. An unsymmetrical cystine peptide was prepared by treatment of a mixture of Z(OMe)-Cys(R) (0)-Ala-NH2 (R = Acm or MBzl) and Z(OMe)-Cys(MBzl)-Gly-OBzl with TFA or 1 M TFMSA/TFA3. Oxytocin was obtained in an excellent yield by TFA treatment of the protected peptide containing Cys(Acm)(0) and Cys(MBzl). Thus, formation of the disulfide bond was found feasible at the position of Cys(R) (0).
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PMID:Studies on peptides CLVIII. Model experiments for the synthesis of open-chain unsymmetrical cystine-peptides. 325 66

The 13C and 15N backbone-labeled proline was prepared using Oppolzer's method based on application of a sultam as chiral auxiliary. This isotopomer was used in the synthesis of the 13C, 15N backbone-labeled C-terminal tripeptide amide fragment of neurohypophyseal hormone oxytocin. Finally, this tripeptide amide was coupled by segment condensation with N-Boc- or N-Fmoc-tocinoic acid, followed by N-deprotection with TFA or piperidine. The labeled oxytocin exhibited biological activity identical with that of natural oxytocin. A detailed 1H, 13C and 15N NMR study confirmed the assigned oxytocin conformation containing a beta-turn in the cyclic part of the molecule, stabilized by H-bond(s) that can be perturbed by the C-terminal tripeptide amide moiety as indicated by comparison of NMR data for both the tocine ring in oxytocin and tocinoic acid.
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PMID:Synthesis and utilization of 13C and 15N backbone-labeled proline: NMR study of synthesized oxytocin with backbone-labeled C-terminal tripeptide amide. 1579 94

Of all the commercially available amino acid derivatives for solid phase peptide synthesis, none has a greater abundance of side-chain protection diversity than cysteine. The high reactivity of the cysteine thiol necessitates its attenuation during peptide construction. Moreover, the propensity of cysteine residues within a peptide or protein sequence to form disulfide connectivity allows the opportunity for the peptide chemist to install these disulfides iteratively as a post-synthetic manipulation through the judicious placement of orthogonal pairs of cysteine S-protection within the peptide's architecture. It is important to continuously discover new vectors of deprotection for these different blocking protocols in order to achieve the highest degree of orthogonality between the removal of one species in the presence of another. We report here a complete investigation of the scope and limitations of the deprotective potential of 2,2'-dithiobis(5-nitropyridine) (DTNP) on a selection of commercially available Cys S-protecting groups. The gentle conditions of DTNP in a TFA solvent system show a remarkable ability to deprotect some cysteine blocking functionality traditionally removable only by more harsh or forcing conditions. Beyond illustrating the deprotective ability of this reagent cocktail within a cysteine-containing peptide sequence, the utility of this method was further demonstrated through iterative disulfide formation in oxytocin and apamin test peptides. It is shown that this methodology has high potential as a stand-alone cysteine deprotection technique or in further manipulation of disulfide architecture within a more complex cysteine-containing peptide template.
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PMID:2,2'-Dithiobis(5-nitropyridine) (DTNP) as an effective and gentle deprotectant for common cysteine protecting groups. 2208 8

The S-acetamidomethyl (Acm) or trityl (Trt) protecting groups are widely used in the chemical synthesis of peptides that contain one or more disulfide bonds. Treatment of peptides containing S-Acm protecting group with iodine results in simultaneous removal of the sulfhydryl protecting group and disulfide formation. However, the excess iodine needs to be quenched or adsorbed as quickly as possible after completion of the disulfide bond formation in order to minimize side reactions that are often associated with the iodination step. We report here a simple method for simultaneous quenching and removal of iodine and isolation of disulphide bridge peptides. The use of excess inexpensive anion exchange resin to the oxidized peptide from the aqueous acetic acid/methanol solution affords quantitative removal of iodine and other color impurities. This improves the resin life time of expensive chromatography media that is used in preparative HPLC column during the purification of peptide using preparative HPLC. Further, it is very useful for the conversion of TFA salt to acetate in situ. It was successfully applied commercially, to the large scale synthesis of various peptides including Desmopressin, Oxytocin, and Octreotide. This new approach offers significant advantages such as more simple utility, minimal side reactions, large scale synthesis of peptide drugs, and greater cost effectiveness.
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PMID:Large Scale Solid Phase Synthesis of Peptide Drugs: Use of Commercial Anion Exchange Resin as Quenching Agent for Removal of Iodine during Disulphide Bond Formation. 2311 72