Total chemical synthesis of the D2 domain of human VEGF receptor 1

Gonçalves, Victor; Gautier, Benoît; Huguenot, Florent; Leproux, P.; Garbay, Christiane; Vidal, Michel; Inguimbert, Nicolas

doi:10.1002/psc.1133

Cited by 9 publications

(10 citation statements)

References 18 publications

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“…However, they are limited to sequences containing serine and threonine at convenient positions. Impressively long peptides have been synthesised using pseudoprolines, notably fas , ubiquitin and D2 domain of vascular endothelial growth factor receptor 1 .…”

Section: Introductionmentioning

confidence: 99%

Advances in Fmoc solid‐phase peptide synthesis

Behrendt

White

Offer

2016

Journal of Peptide Science

563

426

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Today, Fmoc SPPS is the method of choice for peptide synthesis. Very‐high‐quality Fmoc building blocks are available at low cost because of the economies of scale arising from current multiton production of therapeutic peptides by Fmoc SPPS. Many modified derivatives are commercially available as Fmoc building blocks, making synthetic access to a broad range of peptide derivatives straightforward. The number of synthetic peptides entering clinical trials has grown continuously over the last decade, and recent advances in the Fmoc SPPS technology are a response to the growing demand from medicinal chemistry and pharmacology. Improvements are being continually reported for peptide quality, synthesis time and novel synthetic targets. Topical peptide research has contributed to a continuous improvement and expansion of Fmoc SPPS applications. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Advances in Fmoc solid‐phase peptide synthesis

Behrendt

White

Offer

2016

Journal of Peptide Science

563

426

View full text Add to dashboard Cite

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“…Considering the presence of quite regularly distributed Thr and Ser residues in the sequence, we envisioned the possibility to increase the homogeneity of fragment 1 by incorporation of pseudoproline dipeptides, which are well known to reduce the on‐resin self‐association propensity of the growing peptide and, consequently, to improve the quality of the crude product . Accordingly, by using the combination of a polar and low‐loaded resin with the employment of the pseudoproline dipeptides Leu‐445‐ψSer‐446, Phe‐427‐ψSer‐428, and Tyr‐411‐ψSer‐412, the growing chain was ~60% homogeneous after 44 couplings ( 1a TGT+ψ in Scheme B).…”

Section: Resultsmentioning

confidence: 99%

An explorative study towards the chemical synthesis of the immunoglobulin G1 Fc CH3 domain

Grassi

Roschger

Stanojlović

et al. 2018

Journal of Peptide Science

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Monoclonal antibodies, fusion proteins including the immunoglobulin fragment c (Ig Fc) CH2‐CH3 domains, and engineered antibodies are prominent representatives of an important class of drugs and drug candidates, which are referred to as biotherapeutics or biopharmaceuticals. These recombinant proteins are highly heterogeneous due to their glycosylation pattern. In addition, enzyme‐independent reactions, like deamidation, dehydration, and oxidation of sensitive side chains, may contribute to their heterogeneity in a minor amount. To investigate the biological impact of a spontaneous chemical modification, especially if found to be recurrent in a biotherapeutic, it would be necessary to reproduce it in a homogeneous manner. Herein, we undertook an explorative study towards the chemical synthesis of the IgG1 Fc CH3 domain, which has been shown to undergo spontaneous changes like succinimide formation and methionine oxidation. We used Fmoc‐solid‐phase peptide synthesis (SPPS) and native chemical ligation (NCL) to test the accessibility of large fragments of the IgG1 Fc CH3 domain. In general, the incorporation of pseudoproline dipeptides improved the quality of the crude peptide precursors; however, sequences larger than 44 residues could not be achieved by standard stepwise elongation with Fmoc‐SPPS. In contrast, the application of NCL with cysteine residues, which were either native or introduced ad hoc, allowed the assembly of the C‐terminal IgG1 Fc CH3 sequence 371 to 450. The syntheses reported here show advantages and limitations of the chemical approaches chosen for the preparation of the synthetic IgG1 Fc CH3 domain and will guide future plans towards the synthesis of both the native and selectively modified full‐length domain.

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“…The following peptides have been prepared and, therefore, illustrate the usefulness of the approach for such purpose: human amylin [135], [Pro 215 ]-myelin proteolipid protein (PLP) fragment (181-230) and its analog [Ser 215 ]-PLP (181-230) [136], RANTES fragment (1-68) [105], Pan DR epitope [137], insulin-like peptide-3 [138], cecropin (1-7)-melittin (2-9) hybrid, gp41 ectodomain peptide, extended calcipressin fragment with N-terminal extension, CCL4-L1 and CCL4-L2 chemokines [139], and the D2 domain of human vascular endothelial growth factor receptor-1 [140]. The following peptides have been prepared and, therefore, illustrate the usefulness of the approach for such purpose: human amylin [135], [Pro 215 ]-myelin proteolipid protein (PLP) fragment (181-230) and its analog [Ser 215 ]-PLP (181-230) [136], RANTES fragment (1-68) [105], Pan DR epitope [137], insulin-like peptide-3 [138], cecropin (1-7)-melittin (2-9) hybrid, gp41 ectodomain peptide, extended calcipressin fragment with N-terminal extension, CCL4-L1 and CCL4-L2 chemokines [139], and the D2 domain of human vascular endothelial growth factor receptor-1 [140].…”

Section: The Use Of Pseudo-prolinesmentioning

confidence: 99%

Difficult Peptides

Miranda

and

Remuzgo

2010

Amino Acids, Peptides and Proteins in Organic Chemistry

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As thousands of biologically active peptides have been discovered in the last 50 years, to date no one contests that all living organismsfrom bacteria to mammals and complex plant formsproduce such compounds for vital purposes. A few examples are given in Table 16.1.In association with the first discoveries of biologically active peptides, it was noted that natural sources could provide quite restricted amounts of them. At that time, the composition and structure of proteins were not sufficiently understood and the ribosomal machinery remained unknown. Hence, many first-rate chemists started searching for methods, procedures, and protocols that could allow for the preparation of peptides in a variable range of scales and purities. Such circumstances turned peptide synthesis into an important research topic [1,2].In the following decades, peptide synthesis reached a high level of efficacy, and also became a fundamental tool for research in the chemistry and biology of these macromolecules [1,3]. Indeed, most of the current knowledge on peptide hormones, antibiotics, cytotoxins, opioids, and hormone-releasing factors has been generated with the help of synthetics.Peptide synthesis has also been critical for providing a wide range of information in biochemistry, medicine, biology, and chemistry as its applications include: (i) therapeutic purposes [4,5]; (ii) development of techniques for peptide detection, separation, identification, quantification, and analysis [6, 7]; (iii) characterization of proteinase-substrate or inhibitor interactions [8,9]; (iv) study of protein-protein interactions and the basis of protein folding [10,11]; (v) mapping of protein epitopes [12, 13]; (vi) mimicking of enzyme activity [14, 15]; (vii) engineering of new peptide-based drugs with therapeutic potential [16, 17]; (viii) design of new biomaterials [18, 19]; (ix) synthesis of prodrugs [20, 21]; and (x) chemical synthesis of proteins [22, 23].Despite these advances, peptide synthesis remains a research topic that attracts an impressive number of scientists worldwide. Most current studies focus

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Total chemical synthesis of the D2 domain of human VEGF receptor 1

Cited by 9 publications

References 18 publications

Advances in Fmoc solid‐phase peptide synthesis

Advances in Fmoc solid‐phase peptide synthesis

An explorative study towards the chemical synthesis of the immunoglobulin G1 Fc CH3 domain

Difficult Peptides

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