In situ neutralization in boc-chemistry solid phase peptide synthesis: Rapid, high yield assembly of difficult sequences

Simple, effective protocols have been developed for manual and machine-assisted Boc-chemistry solid phase peptide synthesis on polystyrene resins. These use in situ neutralization [i.e. neutralization simultaneous with coupling], high concentrations (> 0.2 M) of Boc-amino acid-OBt esters plus base for rapid coupling, 100% TFA for rapid Boc group removal, and a single short (30 s) DMF flow wash between deprotection/coupling and between coupling/deprotection. Single 10 min coupling times were used throughout. Overall cycle times were 15 min for manual and 19 min for machine-assisted synthesis (75 residues per day). No racemization was detected in the (.)base-catalyzed coupling step. Several side reactions were studied, and eliminated. These included: pyrrolidonecarboxylic acid formation from Gln in hot TFA-DMF; chain-termination by reaction with excess HBTU; and, chain termination by acetylation (from HOAc in commercial Boc-amino acids). The in situ neutralization protocols gave a significant increase in the efficiency of chain assembly, especially for "difficult" sequences arising from sequence-dependent peptide chain aggregation in standard (neutralization prior to coupling) Boc-chemistry SPPS protocols or in Fmoc-chemistry SPPS. Reported syntheses include HIV-1 protease(1-50,Cys.amide), HIV-1 protease(53-99), and the full length HIV-l protease(1-99)

Adaptive self-regulation: A process view of managerial effectiveness

This article describes a set of processes involved in attaining managerial effectiveness. These processes are components of an adaptive self-regulation framework. They involve the active management of constituencies' role expectations and performance opinions through standard-setting, discrepancy-detection, and discrepancy-reduction. These processes serve to enhance constitutents' opinions of the manager's effectiveness. Several social and contextual factors that either facilitate or inhibit managers' self-regulation efforts are identified and hypotheses to guide future empirical research are offered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31730/1/0000669.pd