O-Acyl isopeptides

Y Sohma, M Sasaki, Y Hayashi, T Kimura, Y Kiso. Novel and efficient synthesis of difficult sequence-containing peptides through O-N intramolecular acyl migration reaction of O-acyl isopeptides. Chem Commun 124, 2004. 

An application of the method to Alzheimer s A l-42 revealed that the O-acyl isopeptide of Api-42 (in which the Gly -Ser sequence of A 31-42 was isomerized to a P-ester bond) could be synthesized effectively and stored without spontaneous self-assembly (1-3). Intact monomer A -A2 could then be obtained from the isopeptide under physiologic experimental conditions. The water solubility of the TFA salt of the isopeptide was 100-fold higher than that of A 1 2 (0.14mg mL ). Purified isopeptides could be converted quantitatively... 

Taniguchi A, Sohma Y, Kimura M, Okada T, Ikeda K, Hayashi Y, Kimura T, Hirota S, Matsuzaki K, Kiso Y. Click peptide based on the O-acyl isopeptide method control of Afll-42 production from a photo-triggered Af 1 2 analogue. J. Am. Chem. Soc. 2006 128 696-697. 

Sohma Y, Kiso Y. Click peptides -chemical biology-oriented synthesis of Alzheimer s disease-related amyloid (> peptide (Afl) analogues based on the O-acyl isopeptide method . Chem-BioChem. 2006 7 1549-1557. 

In addition to their use in the in situ induction of conformational transitions, switch-peptides (O-acyl isopeptides) may serve as alternative solubilizing technique in peptide synthesis [207-214]. The elaboration of these concepts, notably the rational design of dynamic pharmacophores as new type of therapeutically useful compounds, is the subject of our current research. 

N-2-hydroxy-4-methoxybenzyl (Hmb) for backbone protection, pseudoprolines and o-acyl isopeptides. 

To overcome aggregation, stepwise elongation of large peptides requires not only potent coupling reagents but also additional tools. In recent years, beneficial results have been obtained by means of PEG resins, pseudoprolines (TPro) and O-acyl isopeptide or depsipeptide methodology. 

Scheme 18.2 Conversion of the O-acyl isopeptide into the N-peptide at pH 7.4.

To prevent racemization, which was one of the limitations of the method (in some cases levels around 20% were reached), pre-formed isodipeptide units, such as Boc-Thr(Fmoc-Val)-OH, were introduced [75], On the basis of these previous results, a completely convergent approach to suppress racemization was also developed [76]. Thus, for a given peptide, an N-terminal fragment, bearing a C-terminal O-acyl isopeptide, was coupled to a C-terminal fragment. Owing to the presence of the urethane-protected Ser/Thr residue, oxazolone formation, and therefore racemization, is avoided. 

O-Acyl isopeptide method, an approach to the efHcient synthesis of peptides containing difficult sequences via the O-N... 

Depsipeptide SPPS methodology, a method for SPPS applicable to difficult sequences arising from aggregation phenomena. It relies on the synthesis of Ser or Thr isopeptide intermediates with a final 0-N acyl migration step. The principle is identical to the O-acyl isopeptide method, also termed click peptide or switch peptide method that were developed independently by different groups. It was, for example, successfully employed to synthesize the extremely difficult WWDomain FBP28 [I. Coin et al.,/. Org. Chem. 2006, 71, 6171]. 

Entries are listed in alphabetical order. The main entry title is printed in bold type, followed by synonyms in bold italics. Numbers, Greek letters and configurational numbers/letters at the beginning of the name are ignored when allocating in alphabetical order, e.g. O-Acyl isopeptide method is listed under A, aj -macroglobulin is listed under M, while 8-quinolyl ester is listed under Q. 

Panda SS, Elagawany M, Marwani HM, Caliskan E, El Khatib M, Oliferenko A, Ahnary KA, Katritzky AR (2014) Chemical ligation from O-acyl isopeptides via 8- and 11-membered cyclic transition states. Arkivoc iv 91-106... 

Panda SS, Oliferenko AA, Marwani HM, Katritzky AR (2014) Effects of preorganization and hydrogen bonding on intramolecular chemical ligation of (A)- and (O)-acyl isopeptides. Mendeleev Commun 24 75-77... 

---