ProtonNMR studies of peptide conformations

Balaram, Padmanabhan

doi:10.1007/bf02839715

Cited by 18 publications

(2 citation statements)

References 44 publications

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“…The concentration effect on spectral appearance can be quite pronounced for ADEP compounds due to their high degree of intramolecular H-bonding in solution. As the concentration is increased, an increased propensity for aggregation in solution occurs due to competing intermolecular H-bonds. This effect is shown at various compound concentrations ( c = 7–35 mg/mL) in the 1 H NMR spectra of 6 (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis and Antibacterial Testing of the A54556 Cyclic Acyldepsipeptides Isolated from Streptomyces hawaiiensis

et al. 2014

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The first total synthesis of all six known A54556 acyldepsipeptide (ADEP) antibiotics from Streptomyces hawaiiensis is reported. This family of compounds has a unique mechanism of antibacterial action, acting as activators of caseinolytic protease (ClpP). Assembly of the 16-membered depsipeptide core was accomplished via a pentafluorophenyl ester-based macrolactamization strategy. Late stage amine deprotection was carried out under neutral conditions by employing a mild hydrogenolysis strategy, which avoids the formation of undesired ring-opened depsipeptide side products encountered during deprotection of acid-labile protecting groups. The free amines were found to be significantly more reactive toward late stage amide bond formation as compared to the corresponding ammonium salts, giving final products in excellent yields. A thorough NMR spectroscopic analysis of these compounds was carried out to formally assign the structures and to aid with the spectroscopic assignment of ADEP analogues. The identity of two of the structures was confirmed by comparison with biologically produced samples from S. hawaiiensis. An X-ray crystallographic analysis of an ADEP analogue reveals a conformation similar to that found in cocrystal structures of ADEPs with ClpP protease. The degree of antibacterial activity of the different compounds was evaluated in vitro using MIC assays employing both Gram-positive and Gram-negative strains and a fluorescence-based biochemical assay.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis and Antibacterial Testing of the A54556 Cyclic Acyldepsipeptides Isolated from Streptomyces hawaiiensis

et al. 2014

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“…27 The "forbidden" nature of CSDs was rst recognized 25 years ago by the research group of Balaram. 28 Although their work focused on the properties of CSDs in synthetic peptides, [29][30][31][32] Balaram et al were also the rst to identify CSDs in crystal structures of natural proteins. [33][34][35][36] Additionally, they recognised that CSDs adopt an unusual conformation, 28 later dubbed the "right-handed staple" 25 (see Fig.…”

Section: Introductionmentioning

confidence: 99%

Between-strand disulfides: forbidden disulfides linking adjacent β-strands

Haworth

Wouters

2013

RSC Adv.

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Between-strand disulfides (BSDs) connect cysteine (Cys) residues across adjacent strands of b-sheets. There are four BSD types which can be found in regular b-structure: CSDs, which link residues immediately opposite each other in the b-structure (residues i and j); ETDs, which connect Cys out of register by one residue (i and j AE 1); BDDs, which join Cys at positions i and j AE 2; and BFDs, which link residues i and j AE 3. Formation of these disulfides was initially predicted to be forbidden, producing too much local strain in the protein fold. However, BSDs do exist in nature. Significantly, their high levels of strain allow them to be involved in redox processes under physiological conditions. Here we characterise BSD motifs found in the Protein Data Bank (PDB), discussing important intrinsic factors, such as the disulfide conformation and torsional strain, and extrinsic factors, such as the influence of the b-sheet environment on the disulfide and vice versa. We also discuss the biological importance of BSDs, including the prevalence of non-homologous examples in the PDB, the conservation of BSD motifs amongst related proteins (BSD clusters) and experimental evidence for BSD redox activity. For clusters of homologous BSDs we present detailed data of the disulfide properties and the variations of these properties amongst the "redundant" structures. Identification of disulfides with the potential to be involved in biological redox processes via the analysis of these data will provide important insights into the function and mechanism of BSD-containing proteins. Characterisation of thiol-based redox signalling pathways will lead to significant breakthroughs in understanding the molecular basis of oxidative stress and associated pathways, such as ageing and neurodegenerative diseases.

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Antiparallel Self‐Association of a γ,α‐Hybrid Peptide: More Relevance of Weak Interactions

Venugopalan

Kishore

2015

Chemistry An Asian Journal

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To learn how a preorganized peptide-based molecular template, together with diverse weak non-covalent interactions, leads to an effective self-association, we investigated the conformational characteristics of a simple γ,α-hybrid model peptide, Boc-γ-Abz-Gly-OMe. The single-crystal X-ray diffraction analysis revealed the existence of a fully extended β-strand-like structure stabilized by two non-conventional C-H⋅⋅⋅O=C intramolecular H-bonds. The 2D (1) H NMR ROESY experiment led us to propose that the flat topology of the urethane-γ-Abz-amide moiety is predominantly preserved in a non-polar environment. The self-association of the energetically more favorable antiparallel β-strand-mimic in solid-state engenders an unusual 'flight of stairs' fabricated through face-to-face and edge-to-edge Ar⋅⋅⋅Ar interactions. In conjunction with FT-IR spectroscopic analysis in chloroform, we highlight that conformationally semi-rigid γ-Abz foldamer in appositely designed peptides may encourage unusual β-strand or β-sheet-like self-association and supramolecular organization stabilized via weak attractive forces.

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ProtonNMR studies of peptide conformations

Cited by 18 publications

References 44 publications

Total Synthesis and Antibacterial Testing of the A54556 Cyclic Acyldepsipeptides Isolated from Streptomyces hawaiiensis

Total Synthesis and Antibacterial Testing of the A54556 Cyclic Acyldepsipeptides Isolated from Streptomyces hawaiiensis

Between-strand disulfides: forbidden disulfides linking adjacent β-strands

Antiparallel Self‐Association of a γ,α‐Hybrid Peptide: More Relevance of Weak Interactions

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