| Range |
Table - link kJ/mol
|
| Organism |
Generic |
| Reference |
Nazaré M et al., Fragment deconstruction of small, potent factor Xa inhibitors: exploring the superadditivity energetics of fragment linking in protein-ligand complexes. Angew Chem Int Ed Engl. 2012 Jan 23 51(4):905-11. doi: 10.1002/anie.201107091. p.909 table 2PubMed ID22190348
|
| Method |
"Here [researchers] explore ?G additivity using two series of small, but very potent inhibitors of a well-characterized and rigid protease as model system. This system allowed [them] to systematically investigate the energetic impact of the linker by a deconstruction analysis into fragments addressing proximal binding sites [ref 12]. [Researchers] recently reported indole-2-carboxamide inhibitors of the serine protease factor Xa (fXa) as central enzyme in the
blood coagulation cascade [ref 13]." |
| Comments |
"Consequently, the fragment deconstruction of 1a and 2a
allowed [researchers] to study detailed contributions to affinity, when
growing molecules from their corresponding fragment into
neighboring subsites. As expected, the most significant
increase is observed, when S1 and S4 fragments are connected
by appropriate linkers. These data on fXa inhibitors and
fragments allows studying the influence of different linkers, as
estimated from summing individual ?G values for fragments
1 and 2 (?Gfrag1, ?Gfrag2) and comparing them to the ?Gfinal of
the final inhibitor (?Glink=?Gfinal-?Gfrag1-?Gfrag2). [Researchers']
analysis is summarized in Table 2 it reveals that linkers
show different effects on the increase of ?Glink." "Table 2 shows the
generation of 1a and 2a by combination of different fragments." See notes beneath table |
| Entered by |
Uri M |
| ID |
111403 |