3ZPT

Design and Synthesis of P1-P3 Macrocyclic Tertiary Alcohol Comprising HIV-1 Protease Inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Design and Synthesis of P1-P3 Macrocyclic Tertiary Alcohol Comprising HIV-1 Protease Inhibitors

Joshi, A.Veron, J.B.Unge, J.Rosenquist, A.Wallberg, H.Samuelsson, B.Hallberg, A.Larhed, M.

(2013) J Med Chem 56: 8999

  • DOI: https://doi.org/10.1021/jm400811d
  • Primary Citation of Related Structures:  
    3ZPS, 3ZPT, 3ZPU

  • PubMed Abstract: 

    To study P1-P3 macrocyclizations of previously reported tertiary-alcohol-comprising HIV-1 protease inhibitors (PIs), three new 14- and 15-member macrocyclic PIs were designed, synthesized by ring-closing metathesis, and evaluated alongside with 10 novel linear PIs. Cocrystallized complexes of the macrocyclic PIs and the HIV-1 protease are presented, analyzed, and discussed. The macrocyclic structures exhibited higher activities than the linear precursors with Ki and EC50 values down to 3.1 nM and 0.37 μM, respectively.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEASE
A, B
99Human immunodeficiency virus 1Mutation(s): 0 
EC: 3.4.23.16
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10))
Explore P03366 
Go to UniProtKB:  P03366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03366
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
M8Y
Query on M8Y

Download Ideal Coordinates CCD File 
F [auth B]methyl N-[(2S)-1-[2-[(4-bromophenyl)methyl]-2-[3-[(3Z,8S,11R)-11-oxidanyl-7,10-bis(oxidanylidene)-8-propan-2-yl-6,9-diazabicyclo[11.2.2]heptadeca-1(16),3,13(17),14-tetraen-11-yl]propyl]hydrazinyl]-3,3-dimethyl-1-oxidanylidene-butan-2-yl]carbamate
C36 H50 Br N5 O6
BWYPGXCADMHJEF-MFVTUPNBSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B],
E [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
M8Y Binding MOAD:  3ZPT Ki: 3.1 (nM) from 1 assay(s)
PDBBind:  3ZPT Ki: 3.1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.54 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.225 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.2α = 90
b = 85.92β = 90
c = 46.27γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-06
    Type: Initial release
  • Version 1.1: 2013-12-11
    Changes: Database references
  • Version 1.2: 2018-01-17
    Changes: Data collection