TY  - JOUR
AU  - Attolino, E.
AU  - Calderone, V.
AU  - Dragoni, E.
AU  - Fragai, M.
AU  - Richichi, B.
AU  - Luchinat, C.
AU  - Nativi, C.
AU  - DESY
TI  - Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).
JO  - European journal of medicinal chemistry
VL  - 45
SN  - 0223-5234
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - PHPPUBDB-20356
SP  - 5919-5925
PY  - 2010
AB  - N-arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water.
KW  - Crystallography, X-Ray
KW  - Matrix Metalloproteinase Inhibitors
KW  - Models, Molecular
KW  - Molecular Structure
KW  - Nanostructures: chemistry
KW  - Protease Inhibitors: chemical synthesis
KW  - Protease Inhibitors: chemistry
KW  - Protease Inhibitors: pharmacology
KW  - Solubility
KW  - Stereoisomerism
KW  - Structure-Activity Relationship
KW  - Sulfones: chemical synthesis
KW  - Sulfones: chemistry
KW  - Sulfones: pharmacology
KW  - Water: chemistry
KW  - Matrix Metalloproteinase Inhibitors (NLM Chemicals)
KW  - Protease Inhibitors (NLM Chemicals)
KW  - Sulfones (NLM Chemicals)
KW  - Water (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:20965620
UR  - <Go to ISI:>//WOS:000285485000044
DO  - DOI:10.1016/j.ejmech.2010.09.057
UR  - https://bib-pubdb1.desy.de/record/97339
ER  -