Constrained Peptides: Models of Bioactive Peptides and Protein Substructures

Rizo, J

doi:10.1146/annurev.biochem.61.1.387

Cited by 48 publications

(86 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, investigation of the biological properties and threedimensional structure of peptides rich in the conformationally restricted C a ,a -disubstituted amino acids is of current interest. Certain C a ,a -dialkylated amino acids have been shown to impart well-defined and predictable conformations to the peptide backbone [4][5][6][7]. These amino acids, in particular a -methylalanine (a-aminoisobutyric acid; Aib), are present in naturally occurring peptide antibiotics [8], conferring a stable helical secondary structure on them and, thereby, ion-transporting properties.…”

Section: Introductionmentioning

confidence: 99%

Proteolytically stable peptides by incorporation of α-Tfm amino acids

et al. 1997

View full text Add to dashboard Cite

A series of model peptides containing alpha-trifluoromethyl-substituted amino acids in five different positions relative to the predominant cleavage site of the serine protease alpha-chymotrypsin was synthesized by solution methods to investigate the influence of alpha-Tfm substitution on the proteolytic stability of peptides. Proteolysis studies demonstrated absolute stability of peptides substituted to the P1 position and still considerable proteolytic stability for peptides substituted at the P2 and P'2 positions compared with the corresponding unsubstituted model peptide. Comparison with peptides containing the fluorine-free disubstituted amino acid alpha-aminoisobutyric acid allowed to separate electronic from steric effects. Furthermore, the absolute configuration of the alpha-Tfm-substituted amino acid was found to exert considerable effects on the proteolytic stability, especially in P'1 substituted peptides. Investigations of this phenomenon using empirical force field calculations revealed that in the (S,R,S)-diasteromer the steric constraints exhibited by the alpha-Tfm group can be outweighed by an advantageous interaction of the flourine atoms with the serine side chain of the enzyme. In contrast, a favourable interaction between substrate and enzyme is impossible for the (S,S,S)-diastereomer.

show abstract

Section: Introductionmentioning

confidence: 99%

Proteolytically stable peptides by incorporation of α-Tfm amino acids

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Synthesis of methyl 2-cyano-3,3-diphenylpropanoate (2). To a slurry of CuI (2.04 g, 10.7 mmol) in dry tetrahydrofuran (70 ml), kept at 0°C under an argon atmosphere, was added dropwise a 3 M solution of phenylmagnesium bromide in dry diethyl ether (75.0 ml, 225 mmol).…”

Section: Synthesesmentioning

confidence: 99%

First synthesis of the two enantiomers of α‐methyldiphenylalanine [(αMe)Dip] by HPLC resolution

et al. 2001

View full text Add to dashboard Cite

A strategy for the preparation of enantiomerically pure (R)- and (S)-alpha-methyldiphenylalanine, constrained phenylalanine analogs, is described. A racemic precursor was prepared in high yield from easily available starting products and subjected to HPLC resolution on a noncommercial chiral stationary phase. More than 600 mg of each enantiomer was isolated in optically pure form by using a 150 x 20 mm ID column containing mixed 10-undecenoate/3,5-dimethylphenylcarbamate of cellulose covalently bonded to allylsilica gel and a mixture of n-hexane/2-propanol/acetone as the mobile phase.

show abstract

“…b-Turns play a crucial role in proteins and bioactive peptides for folding and generating compact structures, [1][2][3] often being involved in molecular recognition processes, [4][5][6] and so is for g-turns, which are considered as rare turns among the types of secondary structures able to reverse the chain direction. 7 b-Turns are a subset of reverse turns and consist of a tetrapeptide sequence in a nonhelical region in which the chain direction is reversed.…”

Section: Introductionmentioning

confidence: 99%

Configurationally driven folding of model tetrapeptides containing L‐ or D‐morpholine‐3‐carboxylic acids as β‐turn nucleators

2008

View full text Add to dashboard Cite

The conformational analysis by NMR, IR, and molecular modeling of tetrapeptides containing morpholine-3-carboxylic acid (Mor) as a proline surrogate is presented. The relationship between the chirality of the cyclic amino acid at position i+1 and the turn propensity is maintained with respect to the reference proline-containing peptides, although marked differences in the type of folded structures were observed. The conformational profile of morpholine-containing turn peptides as a function of the chirality of the cyclic amino acid indicated that the heterochiral tetrapeptide containing the D-isomer of the cyclic amino acid is more prone to nucleate compact folded structures, although with no resemblance to the beta-turn structures of D-proline-containing peptides. Also, the solvation system proved to influence the organization of folded structures, as in the more interactive CD(3)CN the model peptides showed more compact conformations. The L-Mor-containing peptide displayed two rotamers at the Val-Mor amide bond. The trans isomer did not experience any turn structures, nor any intramolecular hydrogen-bonds, whereas the cis isomer showed a strong preference for a type VI beta-turn structure, thus providing a different conformational asset with respect to the beta-turn structure as reported for the reference L-proline model peptide.

show abstract

Constrained Peptides: Models of Bioactive Peptides and Protein Substructures

Cited by 48 publications

References 0 publications

Proteolytically stable peptides by incorporation of α-Tfm amino acids

Proteolytically stable peptides by incorporation of α-Tfm amino acids

First synthesis of the two enantiomers of α‐methyldiphenylalanine [(αMe)Dip] by HPLC resolution

Configurationally driven folding of model tetrapeptides containing L‐ or D‐morpholine‐3‐carboxylic acids as β‐turn nucleators

Contact Info

Product

Resources

About