5513-69-9Relevant articles and documents
Mechanoenzymatic peptide and amide bond formation
Hernández, José G.,Ardila-Fierro, Karen J.,Crawford, Deborah,James, Stuart L.,Bolm, Carsten
supporting information, p. 2620 - 2625 (2017/07/17)
Mechanochemical chemoenzymatic peptide and amide bond formation catalysed by papain was studied by ball milling. Despite the high-energy mixing experienced inside the ball mill, the biocatalyst proved stable and highly efficient to catalyse the formation of α,α- and α,β-dipeptides. This strategy was further extended to the enzymatic acylation of amines by milling, and to the mechanosynthesis of a derivative of the valuable dipeptide L-alanyl-l-glutamine.
Improving the carboxyamidomethyl ester for subtilisin A-catalysed peptide synthesis
De Beer, Roseri J. A. C.,Nuijens, Timo,Wiermans, Lotte,Quaedflieg, Peter J. L. M.,Rutjes, Floris P. J. T.
experimental part, p. 6767 - 6775 (2012/09/22)
A series of novel glycine esters was evaluated for efficiency in subtilisin A-CLEA-catalysed peptide synthesis. The reactivity of the easily accessible carboxyamidomethyl (Cam) ester was further enhanced by elongating it with an amino acid residue, thereby creating more recognition space for subtilisin A.
Enzymatic C-terminal amidation of amino acids and peptides
Nuijens, Timo,Piva, Elena,Kruijtzer, John A.W.,Rijkers, Dirk T.S.,Liskamp, Rob M.J.,Quaedflieg, Peter J.L.M.
experimental part, p. 3777 - 3779 (2012/09/22)
Herein, we describe two versatile and high yielding enzymatic approaches for the conversion of semi-protected amino acid and peptidyl C-terminal α-carboxylic acids into their corresponding amides. In the first approach, the lipase Candida antarctica lipase-B (Cal-B), and in the second approach, the protease Subtilisin A, are used, respectively. We found that by using the ammonium salt of the α-carboxylic acid instead of separate ammonia sources, the enzymatic amidation reactions proceeded much faster without side reactions and gave near to quantitative yields of products.
Papain-Specific Activating Esters in Aqueous Dipeptide Synthesis
de Beer, Roseri J.A.C.,Zarzycka, Barbara,Mariman, Michiel,Amatdjais-Groenen, Helene I.V.,Mulders, Marc J.,Quaedflieg, Peter J.L.M.,van Delft, Floris L.,Nabuurs, Sander B.,Rutjes, Floris P.J.T.
experimental part, p. 1319 - 1326 (2012/08/28)
Enzymatic peptide synthesis has the potential to be a viable alternative for chemical peptide synthesis. Because of the increasing commercial interest in peptides, new and improved enzymatic synthesis methods are desirable. In recently developed enzymatic strategies such as substrate mimetic approaches and enzyme-specific activation, use of the guanidinophenyl ester (OGp) group has been shown to suffer from some drawbacks. OGp esters are sensitive to spontaneous chemical hydrolysis and the group is expensive to synthesize and therefore not suitable for large-scale applications. On the basis of earlier computational studies, we hypothesized that OGp might be replaceable by simpler ester groups to make the enzyme-specific activation approach to peptide bond formation more accessible. To this end, a set of potential activating esters (Z-Gly-Act) was designed, synthesized, and evaluated. Both the benzyl (OBn) and the dimethylaminophenyl (ODmap) esters gave promising results. For these esters, the scope of a model dipeptide synthesis reaction under aqueous conditions was investigated by varying the amino acid donor. The results were compared with those obtained from a previous study of Z-XAA-OGp esters. Computational docking analysis of the set of esters was performed in order to provide insight into the differences in the reactivities of all the potential activating esters. Finally, selected ODmap- and OBn-activated amino acids were applied in the synthesis of two biologically active dipeptides on preparative scales.
Papain-catalyzed peptide bond formation: Enzyme-specific activation with guanidinophenyl esters
de Beer, Roseri J.A.C.,Zarzycka, Barbara,Amatdjais-Groenen, Helene I.V.,Jans, Sander C.B.,Nuijens, Timo,Quaedflieg, Peter J.L.M.,van Delft, Floris L.,Nabuurs, Sander B.,Rutjes, Floris P.J.T.
experimental part, p. 2201 - 2207 (2012/05/05)
The substrate mimetics approach is a versatile method for small-scale enzymatic peptide-bond synthesis in aqueous systems. The protease-recognized amino acid side chain is incorporated in an ester leaving group, the substrate mimetic. This shift of the specific moiety enables the acceptance of amino acids and peptide sequences that are normally not recognized by the enzyme. The guanidinophenyl group (OGp), a known substrate mimetic for the serine proteases trypsin and chymotrypsin, has now been applied for the first time in combination with papain, a cheap and commercially available cysteine protease. To provide insight in the binding mode of various Z-XAA-OGp esters, computational docking studies were performed. The results strongly point at enzyme-specific activation of the OGp esters in papain through a novel mode of action, rather than their functioning as mimetics. Furthermore, the scope of a model dipeptide synthesis was investigated with respect to both the amino acid donor and the nucleophile. Molecular dynamics simulations were carried out to prioritize 22 natural and unnatural amino acid donors for synthesis. Experimental results correlate well with the predicted ranking and show that nearly all amino acids are accepted by papain.
Enzymatic synthesis of activated esters and their subsequent use in enzyme-based peptide synthesis
Nuijens, Timo,Cusan, Claudia,Schepers, Annette C.H.M.,Kruijtzer, John A.W.,Rijkers, Dirk T.S.,Liskamp, Rob M.J.,Quaedflieg, Peter J.L.M.
, p. 79 - 84 (2012/02/03)
Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides. However, there are still some limitations when challenging peptides, e.g. containing sterically demanding acyl donors, non-proteinogenic amino acids or proline residues, are to be synthesized. To remedy these limitations, special ester moieties have been used that are specifically recognized by the enzyme, e.g. guanidinophenyl, carboxamidomethyl (Cam) or trifluoroethyl (Tfe) esters, which, unfortunately, are notoriously difficult to synthesize chemically. Herein, we demonstrate that Cam and Tfe esters are very useful for Alcalase-CLEA mediated peptide synthesis using sterically demanding and non-proteinogenic acyl donors as well as poor nucleophiles, and combinations thereof. Furthermore, these esters can be efficiently synthesized by using the lipase Cal-B or Alcalase-CLEA. Finally, it is shown that the ester synthesis by Cal-B and subsequent peptide synthesis by Alcalase-CLEA can be performed simultaneously using a two-enzyme-one-pot approach with glycolamide or 2,2,2-trifluoroethanol as additive.
Structure-activity relationships of 13-and 14-membered cyclic partial retro-inverso pentapeptides related to enkephalin
Hong, Nam Joo
experimental part, p. 874 - 880 (2010/11/02)
A series of 13-and 14-membered cyclic enkephalin analogs based on the moderately μ selective prototype compound Tyr-C[D-A2bu-Gly-Phe- Leu] 8a were synthesized to investigate the structure-activity relationship. The modifications of sequence were mainly focused on two positions 3 and 5, critical for the selective recognition for μ and δ opioid receptors. The substitution of hydrophobic Leu5 with hydrophilic Asp5 derivatives led to Tyr-C[D-A2bu-Gly-Phe-Asp(N-Me)] 7 and Tyr-C[D-Glu-Phe-gPhe-rAsp(O-Me)] 5, the peptides with a large affinity losses at both μ and δ receptors. The substitution of Phe3 with Gly3 led to Tyr-C[D-Glu-Gly-gPhe-rLeu] 3 and Tyr-C[D-Glu-Gly-gPhe-D- rLeu] 4, the peptides with large affinity losses at μ receptors, indicating the critical role of phenyl ring of Phe3 for μ receptor affinities. One atom reduction of the ring size from 14-membered analogs Tyr-C[D-Glu-Phe-gPhe-(L and D)-rLeu] 6a, 6b to 13-membered analogs Tyr-C[D-Asp-Phe-gPhe-(L and D)-rLeu] 1, 2 reduced the affinity at both μ and δ receptors, but increased the potency in the nociceptive assay, indicating the ring constrain is attributed to high nociceptive potency of the analogs. For the influence of D-or L-chirality of Leu5 on the receptor selectivity, regardless of chirality and ring size, all cyclic diastereomers displayed marked μ selectivity with low potencies at the δ receptor. The retroinverso analogs display similar or more active at μ receptor, but less active at δ receptor than the parent analogs.
C-terminal peptide amidation catalyzed by orange flavedo peptide amidase
Cerovsky, Vaclav,Kula, Maria-Regina
, p. 1885 - 1887 (2007/10/03)
The reverse reaction of amide hydrolysis can be achieved with the peptide amidase derived from oranges [Eq(1); Z=benzyloxycarbonyl]. The C-terminal carboxy group of the peptide is directly converted into an amide group by condensation with an ammonium salt. The amidation of peptides is of major interest since the biological activity of proteohormones and peptides is strongly influenced by the presence of a C-terminal amide group.
A fast procedure for the preparation of amides/peptides from carboxylic acids and azides via two redox reactions: Application to the synthesis of methionine enkephalin
Ghosh, Sunil K.,Verma, Rekha,Ghosh, Usha,Mamdapur, Vasant R.
, p. 1705 - 1711 (2007/10/03)
A one-pot self regulated approach for the synthesis of amides/peptides based on two reduction-oxidation (redox) reactions has been described. The primary and secondary amides/peptides are made by using azidotrimethylsilane and alkyl azides/α-azido acid de
