Enhancement of solubility by temporary dimethoxybenzyl‐substitution of peptide bonds

Blaakmeer, J.; Tijsse-Klasen, T.; Tesser, G. I.

doi:10.1111/j.1399-3011.1991.tb00775.x

Cited by 38 publications

(5 citation statements)

References 21 publications

(4 reference statements)

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“…The observation that the combination of our protocols for SPPS at 60°C25, 26, 32, 33 and CLEAR amide resin49 allowed for obtaining G 113 GGGGYGGGYGGGYGGGKYK 132 ‐NH 2 prompted us to try the total synthesis of our 32‐amino acid residue‐target peptide. Such an attempt, based on peptide backbone protection, could prevent hydrogen bond formation and, consequently, the β‐sheet conformations observed 52–54…”

Section: Resultsmentioning

confidence: 99%

Acanthoscurrin fragment 101–132: Total synthesis at 60°C of a novel difficult sequence

et al. 2008

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Glycine-rich proteins (GRPs) serve a variety of biological functions. Acanthoscurrin is an antimicrobial GRP isolated from hemocytes of the Brazilian spider Acanthoscurria gomesiana. Aiming to contribute to the knowledge of the secondary structure and stepwise solid-phase synthesis of GRPs' glycine-rich domains, we attempted to prepare G(101)GGLGGGRGGGYG(113)GGGGYGGGYG(123) GGY(126)GGGKYK(132)-NH(2), acanthoscurrin C-terminal amidated fragment. Although a theoretical prediction did not indicate high aggregation potential for this peptide, repetitive incomplete aminoacylations were observed after incorporating Tyr(126) to the growing peptide-MBHA resin (Boc chemistry) at 60 degrees C. The problem was not solved by varying the coupling reagents or solvents, adding chaotropic salts to the reaction media or changing the resin/chemistry (Rink amide resin/Fmoc chemistry). Some improvement was made when CLEAR amide resin (Fmoc chemistry) was used, as it allowed for obtaining fragment G(113)-K(132). NIR-FT-Raman spectra collected for samples of the growing peptide-MBHA, -Rink amide resin and -CLEAR amide resin revealed the presence of beta-sheet structures. Only the combination of CLEAR-amide resin, 60 degrees C, Fmoc-(Fmoc-Hmb)Gly-OH and LiCl (the last two used alternately) was able to inhibit the phenomenon, as proven by NIR-FT-Raman analysis of the growing peptide-resin, allowing the total synthesis of desired fragment Gly(101)-K(132). In summary, this work describes a new difficult sequence, contributes to understanding stepwise solid-phase synthesis of this type of peptide and shows that, at least while protected and linked to a resin, this GRP's glycine-rich motif presents an early tendency to assume beta-sheet structures.

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Section: Resultsmentioning

confidence: 99%

Acanthoscurrin fragment 101–132: Total synthesis at 60°C of a novel difficult sequence

et al. 2008

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“…Since SUMO is substantially larger than ubiquitin (SUMO‐1 96 AA versus ubiquitin 76 AA), it was considered to be beyond the limits of linear SPPS. However, we explored the use of “aggregation breakers” such as pseudoproline and dimethoxybenzyl (DMB) residues at strategic positions and devised a synthetic route that takes advantage of the specific building blocks depicted in Figure A. This procedure allowed us to make synthetic SUMO‐1, ‐2, and ‐3 efficiently in a linear fashion.…”

Section: Figurementioning

confidence: 99%

Total Chemical Synthesis of SUMO and SUMO‐Based Probes for Profiling the Activity of SUMO‐Specific Proteases

et al. 2018

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SUMO is ap ost-translational modifier critical for cell cycle progression and genome stability that playsarole in tumorigenesis,t hus rendering SUMO-specific enzymes potential pharmacological targets.H owever,t he systematic generation of tools for the activity profiling of SUMO-specific enzymes has proven challenging.W edeveloped adiversifiable synthetic platform for SUMO-based probes by using ad irect linear synthesis method, which permits N-and C-terminal labelling to incorporate dyes and reactive warheads,r espectively.I nt his manner,a ctivity-based probes (ABPs) for SUMO-1, SUMO-2, and SUMO-3-specific proteases were generated and validated in cells using gel-based assays and confocal microscopy. We further expanded our toolbox with the synthesis of aK 11-linked diSUMO-2 probe to study the proteolytic cleavage of SUMO chains.T ogether,t hese ABPs demonstrate the versatility and specificity of our synthetic SUMO platform for in vitro and in vivo characterization of the SUMO protease family.

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“…Essential amino acids can be identified by screening the biological compatibility peptides in which particular amino acids have been replaced with alanine. Alanine is used due to its small size, moreover, it has uncharged side chains which do not interfere with the activities of adjacent side chains (Blaakmeer et al 1991 ). More complicated scanning methods have been developed over the years which include the enantiomers of amino acids and properties such as hydrophobic or acidic or basic natures are also taken into account.…”

Section: Strategies To Overcome the Limitationsmentioning

confidence: 99%

Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics

Barman

Joshi

Sharma

et al. 2023

Int J Pept Res Ther

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In recent years, the occurrence of a wide variety of drug-resistant diseases has led to an increase in interest in alternate therapies. Peptide-based drugs as an alternate therapy hold researchers’ attention in various therapeutic fields such as neurology, dermatology, oncology, metabolic diseases, etc. Previously, they had been overlooked by pharmaceutical companies due to certain limitations such as proteolytic degradation, poor membrane permeability, low oral bioavailability, shorter half-life, and poor target specificity. Over the last two decades, these limitations have been countered by introducing various modification strategies such as backbone and side-chain modifications, amino acid substitution, etc. which improve their functionality. This has led to a substantial interest of researchers and pharmaceutical companies, moving the next generation of these therapeutics from fundamental research to the market. Various chemical and computational approaches are aiding the production of more stable and long-lasting peptides guiding the formulation of novel and advanced therapeutic agents. However, there is not a single article that talks about various peptide design approaches i.e., in-silico and in-vitro along with their applications and strategies to improve their efficacy. In this review, we try to bring different aspects of peptide-based therapeutics under one article with a clear focus to cover the missing links in the literature. This review draws emphasis on various in-silico approaches and modification-based peptide design strategies. It also highlights the recent progress made in peptide delivery methods important for their enhanced clinical efficacy. The article would provide a bird’s-eye view to researchers aiming to develop peptides with therapeutic applications. Graphical Abstract

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Enhancement of solubility by temporary dimethoxybenzyl‐substitution of peptide bonds

Cited by 38 publications

References 21 publications

Acanthoscurrin fragment 101–132: Total synthesis at 60°C of a novel difficult sequence

Acanthoscurrin fragment 101–132: Total synthesis at 60°C of a novel difficult sequence

Total Chemical Synthesis of SUMO and SUMO‐Based Probes for Profiling the Activity of SUMO‐Specific Proteases

Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics

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