Ligation kinetically controlled

Bang D, Pentelute BL, Kent SBH (2006) Kinetically controlled ligation for the convergent chemical synthesis of proteins. Angew Chem (Engl) 45 3985-3988... 

Scheme 29 Synthesis of a MUCl glycopeptide oligomer using a kinetically-controlled ligation-desulfurization strategy at p-thiol Arg...

Scheme 30 One-pot total synthesis of madanin-1123 using kinetically-controlled ligation-desulfurization chemistry with trifluoroethanethiol (TFET) 124...

In addition of organometallic reagents to some arynes, prior counterion complexation with the substituent can direct the incoming group to the ortho position (kinetic control). Addition of alkyllithiums to oxazolinyl (OXZ) aryne (51) to give the ortho product (52) is explained in this manner. In contrast, lithium dialkylcuprates add to the aryne (51) exclusively at the meta position. This is ascribed to thermodynamic control of the reaction, which results in the formation of the more ligated and stable adduct (S3).i2 Control of nucleophilic addition to arynes by complex-induced proximity effects has not been explored with substituents other than OXZ,83 but has considerable synthetic potential if it can be achieved, say through solvent manipulation. 

Comparisons between R- and T-state hemoglobins on the one hand and a variety of synthetic model compounds on the other have allowed an evaluation of the possible occurrence and importance of electronic, proximal-base tension, and distal-side steric effects on the kinetics of ligation of CO and 02. Although all of these effects could influence the reactivities of hemoproteins, we conclude that hemoglobin reactivity and cooperativity are controlled predominantly by the presence or absence of proximal-base tension. 

The average dimensionless solid phase concentration Y can be given409 the numerical value of 0.5, and if the effect of the film mass transfer is negligible, i.e., if K f - 00, then adsorption with the nonporous HPLC sorbent in a well-packed bed is controlled by second-order kinetics.169,399 When the external film resistance Kf controls the adsorption, equilibrium is assumed to exist between the polypeptide or protein and the polypeptide- or protein-ligate complex at each point on the particle surface. 

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