An Achiral Dipeptide Mimetic That Promotes .beta.-Hairpin Formation

Gardner, Robb R.; Liang, Gui-Bai; Gellman, Samuel H.

doi:10.1021/ja00116a036

Cited by 100 publications

(44 citation statements)

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“…This structure features two intramolecular H-bonds indicated by the dotted lines, in one of which the β-N-H (orange) acts as an H-bond donor and is thus red shifted by ~130 cm −1 from the free δ-N-H group (green). (27, 28) The third N-H is associated with the charge center involved in the intramolecular H-bond and appears near 2700 cm −1 (N-H + in Fig 1a). We can also follow the response of the two H-acceptors, where the carbonyl groups [α(red) and γ(blue)] are found ~85 cm −1 lower than the two free carbonyls [δ (green) and β (orange)].…”

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confidence: 99%

Determination of Noncovalent Docking by Infrared Spectroscopy of Cold Gas-Phase Complexes

Garand

Kamrath

Jordan

et al. 2012

Science

133

126

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Multi-dentate, non-covalent interactions between small molecules and biopolymer fragments are central to processes ranging from drug action to selective catalysis. We present a versatile and sensitive spectroscopic probe of functional groups engaged in hydrogen bonding in such contexts. This involves measurement of the frequency changes in specific covalent bonds upon complex formation, information drawn from otherwise transient complexes that have been extracted from solution and conformationally frozen near 10 Kelvin in gas-phase clusters. Resonances closely associated with individual oscillators are easily identified through site-specific isotopic labeling, as demonstrated by application of the method to an archetypal system involving a synthetic tripeptide known to bind biaryl substrates through tailored H-bonding to catalyze their asymmetric bromination. With such data, calculations readily converge on the plausible operative structures in otherwise computationally prohibitive, high dimensionality landscapes.

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mentioning

confidence: 99%

Determination of Noncovalent Docking by Infrared Spectroscopy of Cold Gas-Phase Complexes

Garand

Kamrath

Jordan

et al. 2012

Science

133

126

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“…Non-hydrogenbonded NϪH bands are typically seen above 3400 cm Ϫ1 , while hydrogen-bonded NϪH bands fall in the 3390Ϫ3330 cm Ϫ1 region. [28,29,30] The figure also shows a remarkable concentration effect taking place above 1 m concentration for the longest oligomer 11. Two additional bands at 3300 Ϯ 20 cm…”

Section: Resultsmentioning

confidence: 91%

Total Synthesis of Sequential Retro‐Peptide Oligomers

et al. 2004

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The total synthesis of sequential oligomers of retro‐peptides of the general formula Boc(‐gGly‐mAib)n‐OBn, starting from dimethylmalonic acid, has been carried out in good overall yield. The key step is the formation of the gGly unit >N−CH2−N<, which is easily obtained in a one‐pot/three‐step reaction from BnO‐mAib‐Gly‐OH and diphenylphosphoryl azide. The synthesis of the sequential oligomers of RCO(‐gAla‐mAib)n‐OR′ was also attempted, but the oligomerization step failed because the gAla moiety readily decomposes or racemizes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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“…In particular, cyclic d-amino acids have been investigated as possible reverse turn mimetics, showing the strict relationship between stereochemistry on the ring system and secondary structure of the sequence containing the d-amino acid. An early example of a linear d-amino acid as a reverse turn inducer was first reported by Gellman et al [58], in which a trans C¼C double bond was introduced to replace the amide bond of the Other authors reported the synthesis and conformational analysis of alkene-based dipeptide isosteres in which the d-amino acid is substituted in the a-and d-positions with methyl groups [59]. The synthetic strategies allow one to obtain d-amino acid (147) in diastereomerically and enantiomerically pure form as a D-Ala-L-Ala isostere via S N 2 0 addition of cuprate reagents to the alkenyl aziridine (148) (Scheme 13.48).…”

Section: D-amino Acids As Reverse Turn Mimeticsmentioning

confidence: 99%

Synthesis of γ‐ and δ‐Amino Acids

Trabocchi

Menchi

Guarna

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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An area of significant importance that provides new dimensions to the field of molecular diversity and drug discovery is the area of peptidomimetics [1]. Biomedical research has reoriented towards the development of new drugs based on peptides and proteins, by introducing both structural and functional specific modifications, and maintaining the features responsible for biological activity. As a part of this research area, unnatural amino acids are of valuable interest in drug discovery and their use as new building blocks for the development of peptidomimetics with a high structural diversity level is of key interest. In particular, medicinal chemistry has taken advantage of the use of amino acid homologs to introduce elements of diversity for the generation of new molecules as drug candidates in the so-called peptidomimetic approach, where a peptide lead is processed into a new nonpeptidic molecule. The additional methylenic unit between the N-and C-termini in b-amino acids results in an increase of the molecular diversity in terms of the higher number of stereoisomers and functional group variety, and many synthetic approaches to the creation of b-amino acids have been published. There is great interest in these as a tool for medicinal chemistry [2] and in the field of b-peptides generally [3]. The g-and d-amino acids have garnered similar interest. In particular, the folding properties of g-[4] and d-peptides [5] have been investigated, as they have been proved to generate stable secondary structures. The homologation of a-amino acids into g-and d-units allows an enormous increase of the chemical diversity within the three and four atoms between the amino and carboxyl groups. Thus, additional substituents and stereocenters expand the number of compounds belonging to the class of g-and d-amino acids. g-Amino acids have been reported both in linear form, and with the amino and carboxyl groups separated or incorporated in a cyclic structure. In the case of d-amino acids, five-and six-membered rings have been mainly reported having two substituents variously tethered between the amino and carboxyl groups. Moreover, bicyclic and spiro compounds have been reported as constrained d-amino acids, especially in the field of peptidomimetics. The synthetic approaches for the preparation of

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An Achiral Dipeptide Mimetic That Promotes .beta.-Hairpin Formation

Cited by 100 publications

References 0 publications

Determination of Noncovalent Docking by Infrared Spectroscopy of Cold Gas-Phase Complexes

Determination of Noncovalent Docking by Infrared Spectroscopy of Cold Gas-Phase Complexes

Total Synthesis of Sequential Retro‐Peptide Oligomers

Synthesis of γ‐ and δ‐Amino Acids

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