2CEN

P1' Extended HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol in the Transition-State Mimicking Scaffold


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.221 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Microwave-Accelerated Synthesis of P1'-Extended HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol in the Transition-State Mimicking Scaffold.

Ekegren, J.K.Ginman, N.Johansson, A.Wallberg, H.Larhed, M.Samuelsson, B.Unge, T.Hallberg, A.

(2006) J Med Chem 49: 1828

  • DOI: https://doi.org/10.1021/jm051239z
  • Primary Citation of Related Structures:  
    2CEJ, 2CEM, 2CEN

  • PubMed Abstract: 

    Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting Ki values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl substituent (EC50 = 0.18-0.22 microM). X-ray crystallographic data were obtained for three inhibitors cocrystallized with the enzyme.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
POL PROTEIN
A, B
99Human immunodeficiency virus 1Mutation(s): 0 
EC: 3.4.23.16
UniProt
Find proteins for Q5RZ09 (Human immunodeficiency virus 1)
Explore Q5RZ09 
Go to UniProtKB:  Q5RZ09
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ5RZ09
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4AH
Query on 4AH

Download Ideal Coordinates CCD File 
C [auth B]{(1S)-1-[N'-[(2S)-2-HYDROXY-2-((1S,2R)-2-HYDROXY-INDAN-1-YLCARBAMOYL)-3-PHENYL-PROPYL]-N'-[4-(PYRIDINE-2-YL)-BENZYL]-HYDRAZINOCARBONYL]-2,2-DIMETHYL-PROPYL}-CARBAMIC ACID METHYL ESTER
C39 H45 N5 O6
QPEXKJZILBODNL-NGXTUNLOSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
4AH PDBBind:  2CEN Ki: 5 (nM) from 1 assay(s)
BindingDB:  2CEN Ki: min: 5, max: 5 (nM) from 2 assay(s)
Binding MOAD:  2CEN Ki: 5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.221 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.35α = 90
b = 85.75β = 90
c = 46.58γ = 90
Software Package:
Software NamePurpose
CNSrefinement
MOSFLMdata reduction
SCALAdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-02-13
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-01-17
    Changes: Data collection
  • Version 1.4: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description