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Folding and Assembly of Short α, ß, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures.
Zhang, Yukun; Zhong, Yulong; Connor, Alan L; Miller, Daniel P; Cao, Ruikai; Shen, Jie; Song, Bo; Baker, Erin S; Tang, Quan; Pulavarti, Surya V S R K; Liu, Rui; Wang, Qiwei; Lu, Zhong-Lin; Szyperski, Thomas; Zeng, Huaqiang; Li, Xiaopeng; Smith, Richard D; Zurek, Eva; Zhu, Jin; Gong, Bing.
Afiliación
  • Zhang Y; Chengdu Institute of Organic Chemistry , Chinese Academy of Sciences , Chengdu 610041 , China.
  • Zhong Y; University of Chinese Academy of Sciences , Beijing 100049 , China.
  • Connor AL; Department of Chemistry , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.
  • Miller DP; Department of Chemistry , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.
  • Cao R; Department of Chemistry , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.
  • Shen J; Department of Chemistry , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.
  • Song B; The NanoBio Lab , 31 Biopolis Way , The Nanos 138669 , Singapore.
  • Baker ES; Department of Chemistry , University of South Florida , Tampa , Florida 33620 , United States.
  • Tang Q; Biological Sciences Division , Pacific Northwest National Laboratory , Richland , Washington 99354 , United States.
  • Pulavarti SVSRK; College of Chemistry , Beijing Normal University , Beijing 100875 , China.
  • Liu R; Department of Chemistry , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.
  • Wang Q; College of Chemistry , Beijing Normal University , Beijing 100875 , China.
  • Lu ZL; Chengdu Institute of Organic Chemistry , Chinese Academy of Sciences , Chengdu 610041 , China.
  • Szyperski T; College of Chemistry , Beijing Normal University , Beijing 100875 , China.
  • Zeng H; Department of Chemistry , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.
  • Li X; The NanoBio Lab , 31 Biopolis Way , The Nanos 138669 , Singapore.
  • Smith RD; Department of Chemistry , University of South Florida , Tampa , Florida 33620 , United States.
  • Zurek E; Biological Sciences Division , Pacific Northwest National Laboratory , Richland , Washington 99354 , United States.
  • Zhu J; Department of Chemistry , University at Buffalo, The State University of New York , Buffalo , New York 14260 , United States.
  • Gong B; Chengdu Institute of Organic Chemistry , Chinese Academy of Sciences , Chengdu 610041 , China.
J Am Chem Soc ; 141(36): 14239-14248, 2019 09 11.
Article en En | MEDLINE | ID: mdl-31381306
ABSTRACT
Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of α-, ß-, and aromatic γ-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, 1 and 2a or 2b, differing only in their central αß hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer 1 folds into an expanded ß-turn containing an unusual hybrid α/ß-amino acid sequence composed of glycine and ß-alanine, two α- and ß-amino acid residues that are conformationally most flexible, and peptides 2a and 2b adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, αß vs ßα, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of 1 and 2. The revealed turn and double helix have few natural or synthetic counterparts, and provide novel and unique folding prototypes based on which chiral α- and ß-amino acids are incorporated. The resultant derivatives 1a, 1b, 2c, and 2d follow the same folding and assembling behavior and demonstrate the generality of this system with the formation of expanded ß-turns and double helices with enhanced folding stabilities, hampered helix inversion, as well as defined and dominant helical sense. This work has demonstrated the unique capability of synthetic foldamers in generating structures with fascinating folding and assembling behavior. The revealed systems offer ample opportunity for further structural optimization and applications.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos Idioma: En Revista: J Am Chem Soc Año: 2019 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos Idioma: En Revista: J Am Chem Soc Año: 2019 Tipo del documento: Article País de afiliación: China