Peptides succinimidyl

NL Benoiton, YC Lee, FMF Chen. A new coupling method allowing epimerization-free aminolysis of segments. Use of succinimidyl esters obtained through mixed anhydrides, in HLS Maia, ed. Peptides 1994. Proceedings of the 23rd European Peptide Symposium, Escom, Leiden, 1995, pp 203-204. 

J Savrda. An unusual side reaction of 1-succinimidyl esters during peptide synthesis. J Org Chem 42, 3199, 1977. 

Further insights into the influence of pH on the reactivity at aspartic acid residues are provided by a study of the model peptide Val-Tyr-Pro-Asp-Gly-Ala (Fig. 6.28,a) [93], At pH 1 and 37°, the tm value for degradation was ca. 450 h, with cleavage of the Asp-Gly bond predominating approximately fourfold over formation of the succinimidyl hexapeptide. At pH 4 and 37°, the tm value was ca. 260 h due to the rapid formation of the succinimidyl hexapeptide, which was slowly replaced by the iso-aspartyl hexapeptide. Cleavage of the Asp-Gly bond was a minor route. At pH 10 and 37°, the tm value was ca. 1700 h, and the iso-aspartyl hexapeptide was the only breakdown product seen. In Sect. 6.3.3.2, we will compare this peptide with three analogues to evaluate the influence of flanking residues. 

The most important degradation mechanism of asparagine and glutamine residues is formation of an intermediate succinimidyl peptide (6.63) without direct backbone cleavage (Fig. 6.29, Pathway e). The reaction, which occurs only in neutral and alkaline media, begins with a nucleophilic attack of the C-neighboring N-atom at the carbonyl C-atom of the Asn side chain (slow step). The succinimide ring epimerizes easily and opens by hydrolysis (fast step), as shown in Fig. 6.27, to yield the iso-aspartyl peptide (6.64) and the aspartyl peptide (6.65) in a ratio of 3 1. 

PEPTID FS Bis(o-nitrophcnyl)pheny 1-phosphonate. Dicydohexylcarbodi-imide. Diphenyl N-succinimidyl phosphate. N-Me t hyl-N-plieny iben/ohyd razor y 1 bromide. n-Propylphosplionic anhydride. Trifluoroniellianesulfonic aeid-Thioanisole. 

Preparation of the amphipathic peptide modified cascade (38, Scheme 7.9) was facilitated by reaction of the polyamine dendrimer with /V-succinimidyl 3-(2-pyridinyldi-thio)propionate (SPDP 36) to give the polypyridinyldisulfide (37). Subsequent treatment of the pyridinyldisulfide moieties with the GALA peptide possessing a cysteine amino acid afforded the modified cascades (38). 

Interpretation of the fragmentation spectra can be difficult and time consuming. It can be simplified if the peptide is modified in such a way that one type of fragmentation is favoured. This can be achieved by derivatizing the amino terminal group with N-succinimidyl-2-(3-pyridyl) acetate, which promotes b fragments [59], Modification of the peptide also can make the distinction between C- and N-terminal fragments easier. 

PEPTIDES 0-Benzotriazolyl-N,N,N, N -letra-methyluronium hexafluorophosphale. l-(3-Dimethylaminopropyl)-3-ethylcarbodi-imide. Di(N-succinimidyl)oxalate. Tetra-... 

Labelling of proteins and peptides with CpRe(CO)3 fragments can be made by peptide bond formation with the carboxylic acid Re(CpCOOH)(CO)3 or by acylation of free amine groups with organometallic succinimidyl esters. 

Bematowicz, M. S. and Matsueda, G. R. (1986) Preparation of peptide-protein immunogens using N-succinimidyl bromoacetate as a heterobifunctional cross-linking reagent. Anal. Biochem. 155, 95-102. 

C-Terminal peptide carbamates are prepared by reaction of the mixed succinimidyl carbonate of the N -protected amino alcohol (e.g., Fmoc-Phe-o-CO-OSu) obtained from the N -protected amino alcohol with DSC in the presence of DMAP, without isolation, with an aminomethyl resin (e.g., H-PAL-Nle-PEG-PSty).f l Standard Fmoc/tBu assembly of the remaining sequence is subsequently performed. Cleavage of the resin with TFA/H2O (19 1) affords the peptide carbamates with good purity. Use of isolated and purified 4-nitrophenyl carbonate monomers has also been described for the same purpose.f l... 

Fredriksson, A., Johnstrom, P., Stone-Elander, S., et al. (2001) Labeling of human C-peptide by conjugation with A-succinimidyl-4-[18F]fluorobenzoate. J Labeled Comp. Radiopharm., 44, 509-519. 

PEPTIDES Bis(o-nitrophenyl)phenyl-phosphonate. Dicyclohexylcarbodi-imide. Diphenyl N-succinimidyl phosphate. N-Methyl-N-phenylbenzohydra-zonyl bromide. n-Propylphosphonic anhydride. Trifluoromethanesulfonic acid-Thioanisole. 

Another peptide derivative of MTX was prepared [362] with the aim of covalently attaching it to antibodies. Condensation of oxidized glutathione tetraethyl ester with 4-amino-4-deoxy-A °-methylpteroic acid with the aid of diethyl phosphorocyanidate afforded the tetraethyl ester (VIII.262) (47% yield). Hydrolysis of the ester groups with Ba(OH)2 followed by ion-exchange chromatography in the presence of 2-mercaptoethanol gave a crude product which was assumed to be the reduced tripeptide. On further purification by gel filtration without 2-mercaptoethanol, this compound underwent spontaneous oxidation to disulphide (VIII.263). In a model experiment, an IgG, monoclonal antibody directed against human transferrin receptor was activated by reaction with A-succinimidyl-3-(2-pyridyldithio)propionate, and con-... 

Attempts to construct peptides by first anchoring the hydroxyl group of serine to the PAC analogue of 2c were less successful because the anchor was labile toward treatment with piperidine. However, the succinimidyl carbonate derivative of hydroxymethyl-PS could be used to anchor serine and... 

Bolton-Hunter Reagent Although not the first to be synthesized, the reagent developed by Bolton and Hunter (Bolton and Hunter, 1973), A -succinimidyl-3-(4-hydroxyphenyl)propionate (Figure 76.6), has found prominent use for the labeling of peptides and small molecules (biotin, melatonin, clonazepam, and so on). 

Figure 6.7-3. Precursors used for residualizing radio-iodination of monoclonal antibodies and peptides. Chemically reactive groups on the precursors are shaded, and site for radio-iodination of the precursor is indicated in black and with an asterisk. SIB N-succinimidyi-3-iodobenzoate SIPC N-succinimidyl 5-iodo-3-pyridinecarboxyiate SGMIB N-succinimidyl 4-guanidinomethyl-3-iodobenzoate.

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