De Novo Design, Synthesis, and X-ray Crystal Structures of Pyrrolinone-Based .beta.-Strand Peptidomimetics

1994 ◽  
Vol 116 (22) ◽  
pp. 9947-9962 ◽  
Author(s):  
Amos B. Smith ◽  
Mark C. Guzman ◽  
Paul A. Sprengeler ◽  
Terence P. Keenan ◽  
Ryan C. Holcomb ◽  
...  
Keyword(s):  
Crystal Structures ◽  
De Novo ◽  
De Novo Design ◽  
Design Synthesis ◽  
Beta Strand ◽  
X Ray

scholarly journals Coiled coils 9-to-5: Rational de novo design of α-helical barrels with tunable oligomeric states

2021 ◽  
Author(s):  
William M. Dawson ◽  
Freddie J.O. Martin ◽  
Guto G. Rhys ◽  
Kathryn L. Shelley ◽  
R. Leo Brady ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Rational Design ◽  
De Novo ◽  
Coiled Coil ◽  
De Novo Design ◽  
Coiled Coils ◽  
Alternative States ◽  
X Ray ◽  
Amphipathic Helices ◽  
Made In

ABSTRACTThe rational design of linear peptides that assemble controllably and predictably in water is challenging. Sequences must encode unique target structures and avoid alternative states. However, the stabilizing and discriminating non-covalent forces available are weak in water. Nonetheless, for α-helical coiled-coil assemblies considerable progress has been made in rational de novo design. In these, sequence repeats of nominally hydrophobic (h) and polar (p) residues, hpphppp, direct the assembly of amphipathic helices into dimeric to tetrameric bundles. Expanding this pattern to hpphhph can produce larger α-helical barrels. Here, we show that pentamers to nonamers are achieved simply by varying the residue at one of these h sites. In L/I-K-E-I-A-x-Z repeats, decreasing the size of Z from threonine to serine to alanine to glycine gives progressively larger oligomers. X-ray crystal structures of the resulting α-helical barrels rationalize this: side chains at Z point directly into the helical interfaces, and smaller residues allow closer helix contacts and larger assemblies.

Artificial Proteins: De novo Design, Synthesis and Solid State Properties

1997 ◽  
pp. 61-99 ◽  
Author(s):  
Jane G. Tirrell ◽  
David A. Tirrell ◽  
Maurille J. Fournier ◽  
Thomas L. Mason
Keyword(s):  
Solid State ◽  
De Novo ◽  
De Novo Design ◽  
Design Synthesis ◽  
Artificial Proteins

scholarly journals Helix packing motif common to the crystal structures of two undecapeptides containing dehydrophenylalanine residues: Implications for the de novo design of helical bundle super secondary structural modules

Biopolymers ◽  
2005 ◽  
Vol 80 (5) ◽  
pp. 617-627 ◽  
Author(s):  
Rudresh ◽  
Madhvi Gupta ◽  
Suryanarayanarao Ramakumar ◽  
Virander S. Chauhan
Keyword(s):  
Crystal Structures ◽  
De Novo ◽  
De Novo Design ◽  
Helical Bundle ◽  
Helix Packing

scholarly journals Inside Cover: De Novo Design, Synthesis and Characterisation of MP3, A New Catalytic Four-Helix Bundle Hemeprotein (Chem. Eur. J. 50/2012)

2012 ◽  
Vol 18 (50) ◽  
pp. 15890-15890
Author(s):  
Marina Faiella ◽  
Ornella Maglio ◽  
Flavia Nastri ◽  
Angela Lombardi ◽  
Liliana Lista ◽  
...  
Keyword(s):  
De Novo ◽  
De Novo Design ◽  
Design Synthesis ◽  
Helix Bundle ◽  
Four Helix Bundle

Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the X-ray crystal structures of their complexes with FKBP12

1993 ◽  
Vol 115 (22) ◽  
pp. 9925-9938 ◽  
Author(s):  
Dennis A. Holt ◽  
Juan I. Luengo ◽  
Dennis S. Yamashita ◽  
Hye Ja Oh ◽  
Arda L. Konialian ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Design Synthesis ◽  
Kinetic Evaluation ◽  
X Ray ◽  
High Affinity

ChemInform Abstract: De Novo Design, Synthesis, and in vitro Evaluation of Inhibitors for Prokaryotic tRNA-Guanine Transglycosylase: A Dramatic Sulfur Effect on Binding Affinity.

ChemInform ◽  
2010 ◽  
Vol 33 (22) ◽  
pp. no-no
Author(s):  
Emmanuel A. Meyer ◽  
Ruth Brenk ◽  
Ronald K. Castellano ◽  
Maya Furler ◽  
Gerhard Klebe ◽  
...  
Keyword(s):  
Binding Affinity ◽  
De Novo ◽  
De Novo Design ◽  
Design Synthesis ◽  
In Vitro Evaluation ◽  
Sulfur Effect

De novo design, synthesis and characterization of membrane active peptides

2001 ◽  
Vol 29 (3) ◽  
pp. A53-A53
Author(s):  
James D. Lear ◽  
Holly Gratkowski ◽  
William F. DeGrado
Keyword(s):  
De Novo ◽  
De Novo Design ◽  
Synthesis And Characterization ◽  
Design Synthesis ◽  
Active Peptides ◽  
Membrane Active Peptides

scholarly journals A defined structural unit enables de novo design of small-molecule–binding proteins

Science ◽  
2020 ◽  
Vol 369 (6508) ◽  
pp. 1227-1233 ◽  
Author(s):  
Nicholas F. Polizzi ◽  
William F. DeGrado
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Small Molecules ◽  
Structural Unit ◽  
De Novo ◽  
Computational Design ◽  
De Novo Design ◽  
X Ray ◽  
X Ray Crystallography ◽  
Chemical Groups

The de novo design of proteins that bind highly functionalized small molecules represents a great challenge. To enable computational design of binders, we developed a unit of protein structure—a van der Mer (vdM)—that maps the backbone of each amino acid to statistically preferred positions of interacting chemical groups. Using vdMs, we designed six de novo proteins to bind the drug apixaban; two bound with low and submicromolar affinity. X-ray crystallography and mutagenesis confirmed a structure with a precisely designed cavity that forms favorable interactions in the drug–protein complex. vdMs may enable design of functional proteins for applications in sensing, medicine, and catalysis.

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