Entrapment of a Water Wire in a Hydrophobic Peptide Channel with an Aromatic Lining

Raghavender, Upadhyayula S.; Chatterjee, Bhaswati; Saha, Indranil; Appavu, Rajagopal; Shamala, Narayanaswamy; Balaram, Padmanabhan

doi:10.1021/jp200462h

Cited by 29 publications

(29 citation statements)

References 49 publications

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“…To overcome these problems, bortezomib analogues are targeted [18]. The peptide based vaccine Nano vaccine adjuvants, and aromatic peptides and beta amino acids are better tool of cancer treatment [19][20][21][22][23][24][25].…”

Section: Side Effects Of Bortezomibmentioning

confidence: 99%

Bortezomib in Anti-Cancer Activity: A Potential Drug

Appavu

Deepa²

2016

Glob J Cancer Ther

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Abstract26S proteasome is an intracellular; ATP dependent enzymatic complex degrades ubiquitin-tagged proteins and maintains cellular homeostasis. The orderly degraded proteins including cyclins, caspases, Bcl-xL, p53, cell adhesion molecules are involved in cell-cycle progression, tumor suppression, DNA replication, inflammation, and apoptosis. So, proteasome inhibition is a target therapy for cancer to promote cell cycle arrest or apoptosis. Bortezomib (Velcade Proteasome inhibitorsA variety of natural and synthetic proteasome inhibitors are available such as peptide aldehydes, peptide α-ketoaldehydes, peptide vinyl sulfones, lactacystin, epoxomicin, peptide macrocycles, γ-lactam thiol ester, epipolythio-dioxopiperazine toxin and eponemycin. But many of these inhibitors are lack in specificity, poor metabolic stability, fast dissociation rate, irreversible and low affinity of binding makes them less suitable for use. For example, peptide aldehyde inhibitors dissociate rapidly and inactivated by oxidization which allows only short-lived proteasome inhibition. These problems overcome by replacing the corresponding aldehyde group in peptides by boronic acid [2]. Because it is forming stable tetrahedral transition state intermediate with N-terminal threonine residue of β5 active site and also peptide boranates dissociate more slowly and attaining stable inhibition [7].

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Section: Side Effects Of Bortezomibmentioning

confidence: 99%

Bortezomib in Anti-Cancer Activity: A Potential Drug

Appavu

Deepa²

2016

Glob J Cancer Ther

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“…These reports sparked a flurry of activity on the conformational properties of β peptide oligomers. An early study from Appavu et al [3][4][5][6][7], had demonstrated that unsubstituted β and γ amino acid residues can be incorporated into oligopeptide helices, without disturbing the overall helical fold [4].…”

Section: H-n I+3mentioning

confidence: 99%

“…Thus, both β-turn and 3 10 /α-helical structures can readily accommodate the Ac 6 c residue. Two β amino acid homologs may be considered viz β 2,2 Ac 6 c, and β 3,3 Ac 6 c. Earlier studies from this laboratory focused on the more readily synthetically accessible residue β 3,3 Ac 6 c. 3,4,5,6,7,8 X-ray crystallographic characterization of a…”

Section: β-Amino Acid Residuesmentioning

confidence: 99%

Introduction of Stereo Chemical Constraints into β -Amino Acid Residues

Chinnasamy¹,

Muthusamy²,

Chinnasamy³

2016

J Vaccines Immunol

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“…Other studies on peptide hairpins containing interacting Phe residues clearly indicate that the energy of interaction of Phe-Phe pairs is about -0.5 kcal/mol compared to its Cha analog [7][8][9]. A study comparing aromatic interactions with salt bridges, demonstrated that the removal of an aromatic ring caused significant hairpin destabilization whereas the replacement of a salt bridge did not cause any major change in peptide stability [10][11][12]. In all these peptides, a consistent edge-to-face geometry was observed indicating that this interaction was preferred despite the conformational flexibility allowed for the side chains of aromatic residues.…”

Section: Aromatic Interactions In Synthetic Peptidesmentioning

confidence: 99%

Nanopeptides: Non - Covalent Interactions in Chemistry and Biological Functions

Selvakkumar¹,

Muthusamy²,

Chinnasamy³

2016

J App Pharm

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The interactions involving the side chains of weakly polar aromatic amino acid residues, e.g., Phenylalanine (Phe), Tyrosine (Tyr) and Tryptophan (Trp) generally reside at the interior of proteins and help in the stabilization of globular protein structures. The aromatic electron cloud of the aromatic rings of these amino acids are delocalized on both sides of the planer rings, so that there is a small partial negative charge on the face and a small partial positive charge on the hydrogen atoms of the edge, which leads to the possibility of electrostatic interactions. These interaction play a vital role nanofiber based vaccine adjuvants, and cocaine vaccine development and increasing interest and structure based drug development. Apart from electrostatic forces, aromatic interactions also consist of van der Waals and hydrophobic forces. These weakly polar interactions are enthalpically comparable to a hydrogen bond. Protein engineering methods have revealed that introducing aromatic pairs and aromatic clusters increases the thermal stability of proteins and it has been demonstrated that the introduction of an additional aromatic interaction improved the thermophilicity and thermostability of the family of 11 xylanase. These weakly polar interactions also have a significant role in the stability of DNA. Different types of weakly polar interactions involving the aromatic side chains are discussed below.Keywords: Aromatic interactions; Peptide; Helix; β -sheet; Dynamics; Folding π…π InteractionThe weakly polar nature of aromatic residues leads to π…π interactions wherein the positively polarized hydrogen atoms of one ring can interact with the δ -π-electron cloud of a second aromatic ring. In 1985, Burley and Petsko observed, "that on an average about 60% of aromatic side chains in proteins are involved in aromatic pairs, 80% of which form networks of three or more interacting aromatic side chains [1][2][3][4][5][6]. Phenyl ring centroids are separated by a preferential distance of between 4.5 Å and 7 Å, and dihedral angles approaching 90° are most common"This π…π interaction has a quadrupole -quadrupole character (distance dependence ~ 1/r 5 ). Subsequently, a large number of analyses of aromatic π…π interactions in the context of peptides as well as in proteins have re-emphasized the importance of aromatic residues in the stability of structures and they have pointed out the occurrence of several potential orientations of closely packed aromatic rings ( Figure 1). The π…π interactions contribute free energy between -0.6 kcal.mol -1 and 1.3 kcal.mol -1 towards the stability of protein structures. It has been suggested from the experiments as well as from the theoretical analysis that van der Waals and the electrostatic forces play important roles in the stability of π…π interactions. Aromatic Interactions in Synthetic PeptidesOne of the earliest monomeric β -hairpins to be examined was derived from the B1 subunit of protein G1. The characteristic stabilizing agent of this peptide was the 'hydrophobic core...

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Entrapment of a Water Wire in a Hydrophobic Peptide Channel with an Aromatic Lining

Cited by 29 publications

References 49 publications

Bortezomib in Anti-Cancer Activity: A Potential Drug

Bortezomib in Anti-Cancer Activity: A Potential Drug

Introduction of Stereo Chemical Constraints into β -Amino Acid Residues

Nanopeptides: Non - Covalent Interactions in Chemistry and Biological Functions

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