Research

Jump to: Review

Open AccessArticle

Lanthanide-Mediated Dephosphorylation Used for Peptide Cleavage during Solid Phase Peptide Synthesis

by

Byunghee Yoo

and

Mark D. Pagel

Molecules 2013, 18(4), 3894-3905; https://doi.org/10.3390/molecules18043894 - 02 Apr 2013

Cited by 3 | Viewed by 5189

Abstract

Lanthanide(III) ions can accelerate the hydrolysis of phosphomonoesters and phosphodiesters in neutral aqueous solution. In this paper, lanthanide-mediated dephosphorylation has been applied in aqueous media as an orthogonal cleavage condition that can be employed in conventional solid phase peptide synthesis (SPPS). A phosphorylated [...] Read more.

Lanthanide(III) ions can accelerate the hydrolysis of phosphomonoesters and phosphodiesters in neutral aqueous solution. In this paper, lanthanide-mediated dephosphorylation has been applied in aqueous media as an orthogonal cleavage condition that can be employed in conventional solid phase peptide synthesis (SPPS). A phosphorylated polymeric support for SPPS was developed using Boc chemistry. The cleavage of resin-bound phosphates was investigated with the addition of Eu(III), Yb(III), acid or base, a mixture of solvents or different temperatures. To demonstrate the utility of this approach for SPPS, a peptide sequence was synthesized on a phosphorylated polymeric support and quantitatively cleaved with lanthanide ions in neutral aqueous media. The protecting groups for side chains were retained during peptide cleavage using lanthanide ions. This new methodology provides a mild orthogonal cleavage condition of phosphoester as a linker during SPPS. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessArticle

A Facile Synthesis of Fully Protected meso-Diaminopimelic Acid (DAP) and Its Application to the Preparation of Lipophilic N-Acyl iE-DAP

by

,

,

and

Molecules 2013, 18(1), 1162-1173; https://doi.org/10.3390/molecules18011162 - 16 Jan 2013

Cited by 11 | Viewed by 5767

Abstract

Synthesis of beneficial protected meso-DAP 9 by cross metathesis of the Garner aldehyde-derived vinyl glycine 1b with protected allyl glycine 2 in the presence of Grubbs second-generation catalyst was performed. Preparation of lipophilic N-acyl iE-DAP as potent agonists of NOD 1-mediated [...] Read more.

Synthesis of beneficial protected meso-DAP 9 by cross metathesis of the Garner aldehyde-derived vinyl glycine 1b with protected allyl glycine 2 in the presence of Grubbs second-generation catalyst was performed. Preparation of lipophilic N-acyl iE-DAP as potent agonists of NOD 1-mediated immune response from 9 is described. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessArticle

Solid Phase versus Solution Phase Synthesis of Heterocyclic Macrocycles

by Seong Jong Kim and

Shelli R. McAlpine

Molecules 2013, 18(1), 1111-1121; https://doi.org/10.3390/molecules18011111 - 16 Jan 2013

Cited by 13 | Viewed by 6591

Abstract

Comparing a solution phase route to a solid phase route in the synthesis of the cytotoxic natural product urukthapelstatin A (Ustat A) confirmed that a solid phase method is superior. The solution phase approach was tedious and involved cyclization of a ridged heterocyclic [...] Read more.

Comparing a solution phase route to a solid phase route in the synthesis of the cytotoxic natural product urukthapelstatin A (Ustat A) confirmed that a solid phase method is superior. The solution phase approach was tedious and involved cyclization of a ridged heterocyclic precursor, while solid phase allowed the rapid generation of a flexible linear peptide. Cyclization of the linear peptide was facile and subsequent generation of three oxazoles located within the structure of Ustat A proved relatively straightforward. Given the ease with which the oxazole Ustat A precursor is formed via our solid phase approach, this route is amenable to rapid analog synthesis. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessArticle

Oxime-Based Carbonates as Useful Reagents for Both N-Protection and Peptide Coupling

by Yahya El-Sayed Jad, Sherine N. Khattab,

Ayman El-Faham

and

Fernando Albericio

Molecules 2012, 17(12), 14361-14376; https://doi.org/10.3390/molecules171214361 - 05 Dec 2012

Cited by 1 | Viewed by 6040

Abstract

We have demonstrated that oxime-based mixed carbonates are very effective reagents for both N-protection and peptide coupling. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessArticle

Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities

by

Margaret W. Ndinguri

,

Manishabrata Bhowmick

,

Dorota Tokmina-Roszyk

,

Trista K. Robichaud

and

Gregg B. Fields

Molecules 2012, 17(12), 14230-14248; https://doi.org/10.3390/molecules171214230 - 30 Nov 2012

Cited by 48 | Viewed by 8393

Abstract

The matrix metalloproteinases (MMPs) exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the [...] Read more.

The matrix metalloproteinases (MMPs) exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the MMP family often take advantage of interactions outside the enzyme active site. We presently focus on peptide-based MMP inhibitors and probes that do not incorporate conventional Zn²⁺ binding groups. In some cases, these inhibitors and probes function by binding only secondary binding sites (exosites), while others bind both exosites and the active site. A myriad of MMP mediated-activities beyond selective catalysis can be inhibited by peptides, particularly cell adhesion, proliferation, motility, and invasion. Selective MMP binding peptides comprise highly customizable, unique imaging agents. Areas of needed improvement for MMP targeting peptides include binding affinity and stability. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview

Applications of Biomaterials to Liquid Crystals

by

,

,

,

and

Molecules 2013, 18(4), 4703-4717; https://doi.org/10.3390/molecules18044703 - 19 Apr 2013

Cited by 41 | Viewed by 6875

Abstract

Nowadays, chemically synthesized proteins and peptides are attractive building blocks and have potential in many important applications as biomaterials. In this review, applications of biomaterials to thermotropic liquid crystals are discussed. The review covers the improvement of the performance of liquid crystal displays [...] Read more.

Nowadays, chemically synthesized proteins and peptides are attractive building blocks and have potential in many important applications as biomaterials. In this review, applications of biomaterials to thermotropic liquid crystals are discussed. The review covers the improvement of the performance of liquid crystal displays using liquid crystal physical gels consisting of a liquid crystal and amino acid-based gelators, and also new functionalization of liquid crystals. Moreover, the influence of DNA, which is one of the more attractive biomaterials, dispersed in thermotropic liquid crystals and its potential use in the liquid crystal industry is described. In addition, we found interesting results during electrooptical measurements of liquid crystals doped with DNA, and explain them from the point of view of biological applications. These recent approaches suggest that these biomaterials may be applicable in the electronic device industry and should be considered as an interesting material with their physical properties having the potential to create or refine an industrial product. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Graphical abstract

Open AccessReview

Chemical Methods for Peptide and Protein Production

by

Saranya Chandrudu

,

Pavla Simerska

and

Istvan Toth

Molecules 2013, 18(4), 4373-4388; https://doi.org/10.3390/molecules18044373 - 12 Apr 2013

Cited by 140 | Viewed by 13690

Abstract

Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling [...] Read more.

Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported a-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessReview

Technologies for the Synthesis of mRNA-Encoding Libraries and Discovery of Bioactive Natural Product-Inspired Non-Traditional Macrocyclic Peptides

by

Kenichiro Ito

,

Toby Passioura

and

Hiroaki Suga

Molecules 2013, 18(3), 3502-3528; https://doi.org/10.3390/molecules18033502 - 18 Mar 2013

Cited by 50 | Viewed by 13573

Abstract

In this review, we discuss emerging technologies for drug discovery, which yields novel molecular scaffolds based on natural product-inspired non-traditional peptides expressed using the translation machinery. Unlike natural products, these technologies allow for constructing mRNA-encoding libraries of macrocyclic peptides containing non-canonical sidechains and [...] Read more.

In this review, we discuss emerging technologies for drug discovery, which yields novel molecular scaffolds based on natural product-inspired non-traditional peptides expressed using the translation machinery. Unlike natural products, these technologies allow for constructing mRNA-encoding libraries of macrocyclic peptides containing non-canonical sidechains and N-methyl-modified backbones. The complexity of sequence space in such libraries reaches as high as a trillion (>10¹²), affording initial hits of high affinity ligands against protein targets. Although this article comprehensively covers several related technologies, we discuss in greater detail the technical development and advantages of the Random non-standard Peptide Integration Discovery (RaPID) system, including the recent identification of inhibitors against various therapeutic targets. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessReview

Synthesis of Peptide Radiopharmaceuticals for the Therapy and Diagnosis of Tumor Diseases

by

Mazen Jamous

,

Uwe Haberkorn

and

Walter Mier

Molecules 2013, 18(3), 3379-3409; https://doi.org/10.3390/molecules18033379 - 14 Mar 2013

Cited by 72 | Viewed by 10833

Abstract

Despite the advances in molecular biology and biochemistry, the prognosis of patients suffering from tumor diseases remains poor. The limited therapeutic success can be explained by the insufficient performance of the common chemotherapeutic drugs that lack the ability to specifically target tumor tissues. [...] Read more.

Despite the advances in molecular biology and biochemistry, the prognosis of patients suffering from tumor diseases remains poor. The limited therapeutic success can be explained by the insufficient performance of the common chemotherapeutic drugs that lack the ability to specifically target tumor tissues. Recently peptide radiopharmaceuticals have been developed that enable the concurrent imaging and therapy of tumors expressing a specific target. Here, with a special emphasis on the synthesis of the building blocks required for the complexation of metallic radioisotopes, the requirements to the design and synthesis of radiolabeled peptides for clinical applications are described. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessReview

3-Substituted Prolines: From Synthesis to Structural Applications, from Peptides to Foldamers

by

,

,

,

,

,

,

,

,

,

and

Molecules 2013, 18(2), 2307-2327; https://doi.org/10.3390/molecules18022307 - 19 Feb 2013

Cited by 37 | Viewed by 10218

Abstract

Among the twenty natural proteinogenic amino acids, proline is unique as its secondary amine forms a tertiary amide when incorporated into biopolymers, thus preventing hydrogen bond formation. Despite the lack of hydrogen bonds and thanks to conformational restriction of flexibility linked to the [...] Read more.

Among the twenty natural proteinogenic amino acids, proline is unique as its secondary amine forms a tertiary amide when incorporated into biopolymers, thus preventing hydrogen bond formation. Despite the lack of hydrogen bonds and thanks to conformational restriction of flexibility linked to the pyrrolidine ring, proline is able to stabilize peptide secondary structures such as b-turns or polyproline helices. These unique conformational properties have aroused a great interest in the development of proline analogues. Among them, proline chimeras are tools combining the proline restriction of flexibility together with the information brought by natural amino acids side chains. This review will focus on the chemical syntheses of 3-substituted proline chimeras of potential use for peptide syntheses and as potential use as tools for SAR studies of biologically active peptides and the development of secondary structure mimetics. Their influence on peptide structure will be briefly described. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Graphical abstract

Open AccessReview

Case Studies of the Synthesis of Bioactive Cyclodepsipeptide Natural Products

by

Sara C. Stolze

and

Markus Kaiser

Molecules 2013, 18(2), 1337-1367; https://doi.org/10.3390/molecules18021337 - 24 Jan 2013

Cited by 23 | Viewed by 6238

Abstract

Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment of [...] Read more.

Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment of a suitable macrocyclization methodology. This review therefore compiles case studies of synthetic approaches to different bioactive cyclodepsipeptide natural products, thereby illustrating obstacles of cyclodepsipeptide synthesis as well as their overcomings. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessReview

Access to Any Site Directed Stable Isotope (²H, ¹³C, ¹⁵N, ¹⁷O and ¹⁸O) in Genetically Encoded Amino Acids

by

Prativa B. S. Dawadi

and

Johan Lugtenburg

Molecules 2013, 18(1), 482-519; https://doi.org/10.3390/molecules18010482 - 02 Jan 2013

Cited by 6 | Viewed by 9246

Abstract

Proteins and peptides play a preeminent role in the processes of living cells. The only way to study structure-function relationships of a protein at the atomic level without any perturbation is by using non-invasive isotope sensitive techniques with site-directed stable isotope incorporation at [...] Read more.

Proteins and peptides play a preeminent role in the processes of living cells. The only way to study structure-function relationships of a protein at the atomic level without any perturbation is by using non-invasive isotope sensitive techniques with site-directed stable isotope incorporation at a predetermined amino acid residue in the protein chain. The method can be extended to study the protein chain tagged with stable isotope enriched amino acid residues at any position or combinations of positions in the system. In order to access these studies synthetic methods to prepare any possible isotopologue and isotopomer of the 22 genetically encoded amino acids have to be available. In this paper the synthetic schemes and the stable isotope enriched building blocks that are available via commercially available stable isotope enriched starting materials are described. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessReview

Semi-Synthesis of Labeled Proteins for Spectroscopic Applications

by

Lucia De Rosa

,

Anna Russomanno

,

Alessandra Romanelli

and

Luca Domenico D'Andrea

Molecules 2013, 18(1), 440-465; https://doi.org/10.3390/molecules18010440 - 02 Jan 2013

Cited by 13 | Viewed by 5802

Abstract

Since the introduction of SPPS by Merrifield in the 60s, peptide chemists have considered the possibility of preparing large proteins. The introduction of native chemical ligation in the 90s and then of expressed protein ligation have opened the way to the preparation of [...] Read more.

Since the introduction of SPPS by Merrifield in the 60s, peptide chemists have considered the possibility of preparing large proteins. The introduction of native chemical ligation in the 90s and then of expressed protein ligation have opened the way to the preparation of synthetic proteins without size limitations. This review focuses on semi-synthetic strategies useful to prepare proteins decorated with spectroscopic probes, like fluorescent labels and stable isotopes, and their biophysical applications. We show that expressed protein ligation, combining the advantages of organic chemistry with the easy and size limitless recombinant protein expression, is an excellent strategy for the chemical synthesis of labeled proteins, enabling a single protein to be functionalized at one or even more distinct positions with different probes. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Graphical abstract

Open AccessReview

Chiral Peptide Nucleic Acids with a Substituent in the N-(2-Aminoethy)glycine Backbone

by

Toru Sugiyama

and

Atsushi Kittaka

Molecules 2013, 18(1), 287-310; https://doi.org/10.3390/molecules18010287 - 27 Dec 2012

Cited by 48 | Viewed by 7543

Abstract

A peptide nucleic acid (PNA) is a synthetic nucleic acid mimic in which the sugar-phosphate backbone is replaced by a peptide backbone. PNAs hybridize to complementary DNA and RNA with higher affinity and superior sequence selectivity compared to DNA. PNAs are resistant to [...] Read more.

A peptide nucleic acid (PNA) is a synthetic nucleic acid mimic in which the sugar-phosphate backbone is replaced by a peptide backbone. PNAs hybridize to complementary DNA and RNA with higher affinity and superior sequence selectivity compared to DNA. PNAs are resistant to nucleases and proteases and have a low affinity for proteins. These properties make PNAs an attractive agent for biological and medical applications. To improve the antisense and antigene properties of PNAs, many backbone modifications of PNAs have been explored under the concept of preorganization. This review focuses on chiral PNAs bearing a substituent in the N-(2-aminoethyl)glycine backbone. Syntheses, properties, and applications of chiral PNAs are described. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Figure 1

Open AccessReview

Chemical Synthesis, Backbone Cyclization and Oxidative Folding of Cystine-knot Peptides — Promising Scaffolds for Applications in Drug Design

by

,

,

and

Molecules 2012, 17(11), 12533-12552; https://doi.org/10.3390/molecules171112533 - 24 Oct 2012

Cited by 35 | Viewed by 12098

Abstract

Cystine-knot peptides display exceptional structural, thermal, and biological stability. Their eponymous motif consists of six cysteine residues that form three disulfide bonds, resulting in a notably rigid structural core. Since they highly tolerate either rational or combinatorial changes in their primary structure, cystine [...] Read more.

Cystine-knot peptides display exceptional structural, thermal, and biological stability. Their eponymous motif consists of six cysteine residues that form three disulfide bonds, resulting in a notably rigid structural core. Since they highly tolerate either rational or combinatorial changes in their primary structure, cystine knots are considered to be promising frameworks for the development of peptide-based pharmaceuticals. Despite their relatively small size (two to three dozens amino acid residues), the chemical synthesis route is challenging since it involves critical steps such as head-to-tail cyclization and oxidative folding towards the respective bioactive isomer. Herein we describe the topology of cystine-knot peptides, their synthetic availability and briefly discuss potential applications of engineered variants in diagnostics and therapy. Full article

(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Special Issue "Chemical Protein and Peptide Synthesis"

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (15 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI