X-Ray crystal structure of pivaloyl-<scp>D</scp>-Pro-<scp>L</scp>-Pro-<scp>L</scp>-Ala-N-methylamide; observation of a consecutive β-turn conformation

Nair, C. Mohanakumaran; Vijayan, M.; Venkatachalapathi, Y. V.; Balaram, Padmanabhan

doi:10.1039/c39790001183

Cited by 66 publications

(67 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tetrapeptide is a consensus sequence designed to adopt a type II’β-turn. 28 In solution at neutral pH, SVS-1 should adopt an ensemble of random coil conformations where the turn region of the peptide is structured, but the appended strand regions are largely unstructured, Figure 1. In the absence of any compensatory interactions, the high density of positive charge from the lysine side chains, results in intra-strand charge repulsion, keeping the N- and C-terminal strands from interacting to form the folded β-hairpin.…”

Section: Resultsmentioning

confidence: 99%

Anticancer β-Hairpin Peptides: Membrane-Induced Folding Triggers Activity

Sinthuvanich

Veiga

Gupta³

et al. 2012

J. Am. Chem. Soc.

155

160

View full text Add to dashboard Cite

Several cationic antimicrobial peptides (AMPs) have recently been shown to display anticancer activity via a mechanism that usually entails the disruption of cancer cell membranes. In this work, we designed an 18-residue anticancer peptide, SVS-1, whose mechanism of action is designed to take advantage of the aberrant lipid composition presented on the outer leaflet of cancer cell membranes, which makes the surface of these cells relatively electronegative relative to non-cancerous cells. SVS-1 is designed to remain unfolded and inactive in aqueous solution but preferentially fold at the surface of cancer cells, adopting an amphiphilic β-hairpin structure capable of membrane disruption. Membrane-induced folding is driven by electrostatic interaction between the peptide and the negatively charge membrane surface of cancer cells. SVS-1 is active against a variety of cancer cell lines such as A549 (lung carcinoma), KB (epidermal carcinoma), MCF-7 (breast carcinoma) and MDA-MB-436 (breast carcinoma). However, the cytotoxicity towards non-cancerous cells having typical membrane compositions, such as HUVEC and erythrocytes, is low. CD spectroscopy, appropriately designed peptide controls, cell-based studies, liposome leakage assays and electron microscopy support the intended mechanism of action, which leads to preferential killing of cancerous cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Anticancer β-Hairpin Peptides: Membrane-Induced Folding Triggers Activity

Sinthuvanich

Veiga

Gupta³

et al. 2012

J. Am. Chem. Soc.

155

160

View full text Add to dashboard Cite

show abstract

“…In the construction of the so called protein epitope mimetic, a d -Pro- l -Pro template was used to induce and stabilize the β-hairpin conformation that is present in Fc-III [68]. Computer mimetic design modeled on Fc-III and the d -Pro- l -Pro template afforded two mimetics, FcBP-1 and FcBP-2 (Figure 4).…”

Section: Immunoglobulin Binding Peptides and Peptidomimeticsmentioning

confidence: 99%

Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

2016

View full text Add to dashboard Cite

The rapidly increasing application of antibodies has inspired the development of several novel methods to isolate and target antibodies using smart biomaterials that mimic the binding of Fc-receptors to antibodies. The Fc-binding domain of antibodies is the primary binding site for e.g., effector proteins and secondary antibodies, whereas antigens bind to the Fab region. Protein A, G, and L, surface proteins expressed by pathogenic bacteria, are well known to bind immunoglobulin and have been widely exploited in antibody purification strategies. Several difficulties are encountered when bacterial proteins are used in antibody research and application. One of the major obstacles hampering the use of bacterial proteins is sample contamination with trace amounts of these proteins, which can invoke an immune response in the host. Many research groups actively develop synthetic ligands that are able to selectively and strongly bind to antibodies. Among the reported ligands, peptides that bind to the Fc-domain of antibodies are attractive tools in antibody research. Besides their use as high affinity ligands in antibody purification chromatography, Fc-binding peptides are applied e.g., to localize antibodies on nanomaterials and to increase the half-life of proteins in serum. In this review, recent developments of Fc-binding peptides are presented and their binding characteristics and diverse applications are discussed.

show abstract

“…The valine residue contains a β-branched side chain that stabilizes a trans amide bond between it and the successive D-proline[52]. The D- and L-proline residues at positions i +1 and i +2 adopt dihedral angles that ensure reversal of the main chain when peptide folding is initiated[53]. The threonine at position i +4 is designed to stabilize the folded turn via hydrogen bond formation between its side chain alcohol and the main-chain carbonyl of the valine at position i (not shown in Figure)[54].…”

Section: Resultsmentioning

confidence: 99%

Design of self-assembling peptide hydrogelators amenable to bacterial expression

Sönmez¹,

Nagy²

2015

Biomaterials

View full text Add to dashboard Cite

Hydrogels formed from self-assembling peptides are finding use in tissue engineering and drug delivery applications. Given the notorious difficulties associated with producing self-assembling peptides by recombinant expression, most are typically prepared by chemical synthesis. Herein, we report the design of a family of self-assembling β-hairpin peptides amenable to efficient production using an optimized bacterial expression system. Expressing peptides, EX1, EX2 and EX3 contain identical eight-residue amphiphilic β-strands connected by varying turn sequences that are responsible for ensuring chain reversal and the proper intramolecular folding and consequent self-assembly of the peptide into a hydrogel network under physiological conditions. EX1 was initially used to establish and optimize the bacterial expression system by which all the peptides could be eventually individually expressed. Expression clones were designed to allow exploration of possible fusion partners and investigate both enzymatic and chemical cleavage as means to liberate the target peptide. A systematic analysis of possible expression systems followed by fermentation optimization lead to a system in which all three peptides could be expressed as fusions with BAD-BH3, the BH3 domain of the proapoptotic BAD (Bcl-2 Associated Death) Protein. CNBr cleavage followed by purification afforded 50, 31, and 15 mg/L yields of pure EX1, EX2 and EX3, respectively. CD spectroscopy, TEM, and rheological analysis indicate that these peptides fold and assembled into well-defined fibrils that constitute hydrogels having shear-thin/recovery properties.

show abstract

X-Ray crystal structure of pivaloyl-D-Pro-L-Pro-L-Ala-N-methylamide; observation of a consecutive β-turn conformation

Cited by 66 publications

References 0 publications

Anticancer β-Hairpin Peptides: Membrane-Induced Folding Triggers Activity

Anticancer β-Hairpin Peptides: Membrane-Induced Folding Triggers Activity

Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

Design of self-assembling peptide hydrogelators amenable to bacterial expression

Contact Info

Product

Resources

About