Acyl peptide

Gripon P, Cannie I, Urban S (2005). EfScient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein. J Virol 79 1613-1622 Harris RS, Liddament MT (2004) Retroviral restriction by APOBEC proteins. Nat Rev Immunol 4 868-877... 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

Kojima, M Hosoda, H., Date, Y. et al. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656-60. 

The acylated peptides (Myr)GCX-Bimane 31 a-e (X = G, L, R, T, V), which are found in certain nonreceptor tyrosine kinases and ct-subunits of several heterotrimeric G-proteins, were synthesized in solution using common solution-phase peptide synthesis with X-myristoylglycine as a building block. These model peptides were used for acylation studies with palmitoyl-CoA in phospholipid vesicles at physiological pH. For such uncatalyzed spontaneous reactions only a modest molar excess of acyl donor species (2.5 1) was necessary. Unprotected side chains of threonine or serine are not interfering with this S-acylation (Scheme 14). 

A-Acyl peptides 277 containing an a,a-di(isopropylthio)glycine residue have also been described. These compounds were prepared as shown in Scheme 7.89. Thus, a 4,4-di(isopropylthio)-2-substituted-5(4//)-oxazolone 276 was prepared from a 2-substituted-5(4//)-oxazolone 275 by reaction with A-(isopropylsulfenyl)-succinimide. The starting 2-substituted-5(4//)-oxazolone was prepared by cychza-tion of an A-acylglycine. °... 

Unfortunately, A-(9-fluorenylmethoxycarbonyl)aziridine-2-carboxylic acid cannot be used in peptide synthesis, since N-deprotection of the respective peptides with secondary amines leads to oxazoline or dehydroamino acid side products. Similarly, N-(tert-butoxy-carbonyl)aziridine-2-carboxylic acid is inappropriate due to the instability of the aziridine moiety to TFA treatment. Attempts to convert A-tritylaziridine-2-carboxylic acid into homogenous and stable active esters as useful intermediates in peptide synthesis leads to positive results only in the case of the pentafluorophenyl ester. 47 Consequently, this active ester seems to be the method of choice for acylating peptides. The related Abhydroxysuc-cinimide and A-3-hydroxy-4-oxo-3,4-dihydro-l,2,3-benzotriazine ester could not be isolated in pure form and have therefore been used as crude products. 47 Access to 2-carbonylazir-idine peptides is also possible by carbodiimide-mediated coupling. Additionally, alkylamides of A-tritylaziridine-2-carboxylic acid are prepared by the azide method,1 5 yet this method fails in peptide coupling steps. 85 ... 

Scheme 15 Route to Cyclic Depsipeptides through Acyl Peptide Cesium Salt 1161...

In general thioesters can be prepared in solution by simple coupling of the N-protected amino acid or peptide with a thiol or a S-acylated peptide in the presence of the following activating systems, DCC/HOBt, EDC/HOBt, or CDI (Scheme ll). 6,75,76 ... 

Geht man von optisch aktiven N-Acyl-aminosauren aus, so werden ohne besondere VorsichtsmaBregeln meist racemische A2-Oxazolinone erhalten. Optisch aktive A2-Oxazolinone und N-Acyl-peptid-oxazolinone konnen nach der Dicyclohexylcarbodiimid-Methode 74,81,149,156) 0(jer durch Behandeln von N-Acyl-aminosauren und -peptiden mit Acetanhydrid/ Dioxan unter genau definierten Bedingungen 74,76) dargestellt werden. 

F Schauwecker, F Pfennig, N Grammel, U Keller. Construction and in vitro analysis of a new bi-modular polypeptide synthetase for synthesis of N-methylated acyl peptides. Chem Biol 7 287-297, 2000. 

Our initial applications of the stepped collision energy LC-ESMS approach involved selective detection (and differentiation) of N- or O-glycosylated peptides (5,6), and detection of phosphorylated peptides (7,8,11). The method has been in routine use in our laboratory for over two years and during this time has become one of the mainstays of our work in characterizing protein modifications. Here we present some of our more recent studies on protein glycosylation and phosphorylation, and illustrate a preliminary evaluation of the stepped collision energy LC-ESMS method for selective detection of sulfated and acylated peptides in protein digests. 

Remarkable advances have been made in the synthesis of N- and O-glycosylated amino acids that, in addition to the 5-fattyacyl-cysteine, are the most sensitive derivatives to the conditions of peptide synthesis. The fine tuning of both carbohydrate and peptide chemistry as well as the use of enzymatic methods are required for the synthesis of glycopeptides. " Similarly soft chemistry has to be applied in the case of S-acylated peptides, whereas fat-tyacylation at amino groups raises no additional difficulties.The state of the art in the field of glyco- and lipopeptide synthesis is discussed in details in Vol. E22b, Sections 6.3 and 6.4, respectively. 

Several factors affect the volatility and stability of a peptide derivative, not least of these being the number and nature of the constituent amino acids. Heterocyclic and aromatic amino acids reduce volatility while those containing sulphur tend to decrease the thermal stability. Small naturally occurring peptides which are not derived from proteins often contain only aliphatic amino acids which lack functional groups in the side chains. Peptides of this type of up to about ten amino acids, after conversion to suitable derivatives, are amenable to analysis by mass spectrometry, e.g. [164]. A variety of derivatives has been reported and include N-trifluoroacetyl peptide esters [136,165], N-acetyl peptide esters [166-168], aromatic N-acyl peptide esters [169-172], and per-methylated N-acyl peptides [173]. The principal modes of the electron impact induced fragmentation of these peptide derivatives are well established and have been summarised in recent reviews [174,175]. Although the spectra of the permethylated derivatives [176] are perhaps the simplest and easiest to interpret and are now frequently used, the N-acyl peptide esters have been widely and successfully employed. 

Prepared from catechol and phosphorus trichloride via o-phenylenephosphoro-chloridite. Used in peptide synthesis for the direct interaction of the two com-ponents (compare tetraethyl pyrophosphite). Synthesis of dipeptides is satisfactory, but extensive racemization occurs when N-acyl peptides are employed. 

The reagent reacts with the Iriethyiamine salt of an N -acylated peptide to form a mixed anhydride, which decomposes to an acyl thiohydantoin bearing a substituent group identifying the amino acid at the carboxyl end of the peptide chain. ... 

It is many years since Schlack and Kumpf showed that a simple A-acyl peptide treated with ammonium thiocyanate and acetic anhydride (Scheme 5.7) underwent cyclisation at the C-terminus to yield l-acyl-2-thiohydantoins (5.29). Mild alkaline hydrolysis then yielded the 2-thiohydantoin (5.30) corresponding to the C-terminal terminal residue and an A-acylpeptide containing one amino acid fewer. This reaction sequence should lead to a cyclic procedure at the C-terminus analogous to the Edman procedure at the A-terminus. Despite several attempts to avoid side reac-... 

Modification by acylation Acylation is the conjugation of an acylchain to the proteins (129,130). The rationale for acylating peptides is alteration in the circulation time and increased stability against degradation. One of the protein products on market is an insulin product, Levemir (Novo Nordisk). Determir has an increased circulation time due to the attachment to serum albumin approximately 98% is bound (129,144,145). In Determir, a C-14 acylchain is attached to insulin at B29. Another product in Phase 3 trials is... 

DEPC in combination with NEtj has proved to be a new efficient reagent for the direct C-formylation of active methylene compounds with carboxylic acids and also for the iV-acylation (peptide bond formation), 5-acylation (thioester formation) and O-acylation (esterification).4,5 Reaction of DEPC with carboxylic acids 11 in the presence of triethylamine produces transient acyl cyanides, which in the presence of alcohols or thiols results in the formation of the corresponding esters (12) or thioesters (13). 

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