A<i>cis</i>Amide Bond Surrogate Incorporating 1,2,4-Triazole

Hitotsuyanagi, Yukio; Motegi, Shuichi; Fukaya, Haruhiko; Takeya, Koichi

doi:10.1021/jo010904i

Cited by 84 publications

(41 citation statements)

References 16 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the latter, a synthetically demanding conformation-restriction method has to be used to obtain the thermodynamically unfavorable cis conformers. [11,12] Here we prove that significant photoswitching occurs with secondary thiopeptide bonds and, more importantly, that the secondary thiopeptide bond can undergo dual-directional photoswitching, that is, it can be photoswitched from the trans conformation to the cis conformation and vice versa; this is different to the situation with the reported N-alkyl thiopeptide bonds.…”

Section: Introductioncontrasting

confidence: 53%

cis/trans Photoisomerization of Secondary Thiopeptide Bonds

Zhao

Micheau

Vargas

et al. 2004

Chemistry A European J

View full text Add to dashboard Cite

The reversible cis/trans photoisomerization of secondary thiopeptide bonds has been systematically studied with UV-visible absorption, capillary electrophoresis, 1H NMR spectroscopy, and circular dichroism methods. It was found that the concentration of the cis conformers could be increased from less than 1 % in the thermal equilibrated solution to up to 20 % in the photostationary state. The rotational barriers of the thiopeptide bond and the pH dependence of the isomerization rates were also studied. The quantum yields of the trans-->cis and the cis-->trans processes were determined from photokinetic analysis.

show abstract

Section: Introductioncontrasting

confidence: 53%

cis/trans Photoisomerization of Secondary Thiopeptide Bonds

Zhao

Micheau

Vargas

et al. 2004

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Several peptidomimetic approaches mimic type VI -turns by stabilizing the cis-amide bond by incorporating the 1,5-disubstituted tetrazole ring, [14][15][16][17][18][19][20] the 1,2,5-triazole, 21 or 1,2,4-triazole 22 as a cis-amide bond surrogate (Scheme 1a); incorporating vicinal disulfide bonds, [23][24][25][26][27] bicyclic dipeptide analogs, 11,[28][29][30][31][32][33][34][35] and certain sequences into cyclic peptides 36 (Scheme 1b). Alternatively, based on the unique role of proline residues in cis-trans isomerization and proline's high frequency as the central residue of -turns, several different strategies have been employed to stabilize the cis-amide bond through directly modifying proline residues: substituting sterically bulky groups on the C of proline [37][38][39][40][41][42][43][44] (Scheme 1c); introducing oxaproline (oxaPro) or thioproline (thioPro), the oxazolidine-or thiazolidine-derived proline analogs 10,[45][46][47][48][49] (Scheme 1d); and incorporating the amino acid analog azaproline (azPro), [50][51][52][53][54]…”

Section: Introductionmentioning

confidence: 99%

Impact of Cis‐proline analogs on peptide conformation

Che

Marshall

2005

Biopolymers

View full text Add to dashboard Cite

The beta-turn is a common motif in both proteins and peptides and often a recognition site in protein interactions. A beta-turn of four sequential residues reverses the direction of the peptide chain and is classified by the phi and psi backbone torsional angles of residues i + 1 and i + 2. The type VI turn usually contains a proline with a cis-amide bond at residue i + 2. Cis-proline analogs that constrain the peptide to adopt a type VI turn led to peptidomimetics with enhanced activity or metabolic stability. To compare the impact of different analogs on amide cis-trans isomerism and peptide conformation, the conformational preference for the cis-amide bond and the type VI turn was investigated at the MP2/6-31+G** level of theory in water (polarizable continuum water model). Analogs stabilize the cis-amide conformations through different mechanisms: (1) 5-alkylproline, with bulky hydrocarbon substituent on the C(delta) of proline, increases the cis-amide population through steric hindrance between the alkyl substituent and the N-terminal residues; (2) oxaproline or thioproline, the oxazolidine- or thiazolidine-derived proline analog, favors interactions between the dipole of the heterocyclic ring and the preceding carbonyl oxygen; and (3) azaproline, containing a nitrogen atom in place of the C(alpha) of proline, prefers the cis-amide bond by lone-pair repulsion between the alpha-nitrogen and the preceding carbonyl oxygen. Preference for the cis conformation was augmented by combining different modifications within a single proline. Azaproline and its derivatives are most effective in stabilizing cis-amide bonds without introducing additional steric bulk to compromise receptor interactions.

show abstract

“…14 Another interesting application of triazole was to employ it as a cis-amide bond surrogate. 15 Replacement of the Ala-NMe-Tyr(OMe) amide bond in RA-VII, a plant-origin anti-tumor bicyclic hexapeptide, with [1,2,4]triazole yielded michael_chorev@hms.harvard.edu. SUPPORTING INFORMATION: General procedures for synthesis, 1 HNMR of 3a, 3c, 4a, 4b, 4c, 4k, 6c, 6d, 7d and 6f; 13 CNMR of 3a, 4a, 4b, 4k, 6c, 7d and 6f; LCMS of 3c, 4c, 6d-7d regioisomeric mixture and 6e-7e regioisomeric mixture and NOESY and TOCSY of 6c, 6f and 6g.…”

Section: Introductionmentioning

confidence: 99%

“…15 This reaction proceeds through the formation of acyl hydrazide adduct which is cyclized to the corresponding [1,2,4]triazole under acidic conditions. However, the problem in extending this methodology for the thiourea lies in the regioselectivity of the cyclization (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Synthetic Studies toward Aryl-(4-aryl-4H-[1,2,4]triazole-3-yl)-amine from 1,3-Diarylthiourea as Urea Mimetics

et al. 2005

View full text Add to dashboard Cite

A thiophile promoted synthesis of di-substituted 4H-[1,2,4]triazole-3-yl-amines as urea mimetics from the corresponding 1,3-disubstituted thioureas has been studied and the scope and limitations of this reaction are presented. The reaction proceeds through the formation of a carbodiimide, followed by a sequential addition-dehydration with acyl hydrazides. 1,3-Branched dialkylthioureas result in the formation of the corresponding ureas. The electronic and steric effect of the substitution on the phenyl rings of the 1,3-diarylthioureas play an important role in the formation of the intermediary carbodiimde and the direction of the subsequent ring closure of the N-acyl hydrazide adduct.

show abstract

AcisAmide Bond Surrogate Incorporating 1,2,4-Triazole

Abstract: A novel cis amide bond surrogate incorporating 1,2,4-triazole was designed and synthesized by the reaction of a thionotripeptide, formic hydrazide, and mercury(II) acetate. This method of surrogate formation was also applicable to a cyclic thionopeptide.

Cited by 84 publications

References 16 publications

cis/trans Photoisomerization of Secondary Thiopeptide Bonds

cis/trans Photoisomerization of Secondary Thiopeptide Bonds

Impact of Cis‐proline analogs on peptide conformation

Synthetic Studies toward Aryl-(4-aryl-4H-[1,2,4]triazole-3-yl)-amine from 1,3-Diarylthiourea as Urea Mimetics

Contact Info

Product

Resources

About