Site-selective C-C modification of proteins at neutral pH using organocatalyst-mediated cross aldol ligations

The bioconjugation of proteins with small molecules has proved an invaluable strategy for probing and perturbing biological mechanisms. The general use of chemical methods for protein functionalisation can be limited however by the requirement for complicated reaction partners to be present in large excess, and harsh conditions which are incompatible with many protein scaffolds. Herein we describe a site-selective organocatalyst-mediated protein aldol ligation (OPAL) that affords stable carbon-carbon linked bioconjugates at neutral pH. OPAL enables rapid modification of proteins using simple aldehyde probes in minimal excess, and is utilised here in the affinity tagging of proteins in cell lysate. Furthermore we demonstrate that the β-hydroxy aldehyde OPAL product can be functionalised again at neutral pH in a tandem organocatalyst-mediated oxime ligation. This tandem strategy is showcased in the ‘chemical mimicry’ of a previously inaccessible natural dual post-translationally modified protein integral to the pathogenesis of the neglected tropical disease Leishmaniasis

Quantum mechanics/molecular mechanics studies on the mechanism of action of cofactor pyridoxal 5'-phosphate in ornithine 4,5-aminomutase

A computational study was performed on the experimentally elusive cyclisation step in the cofactor pyridoxal 5′-phosphate (PLP)-dependent D-ornithine 4,5-aminomutase (OAM)-catalysed reaction. Calculations using both model systems and a combined quantum mechanics/molecular mechanics approach suggest that regulation of the cyclic radical intermediate is achieved through the synergy of the intrinsic catalytic power of cofactor PLP and the active site of the enzyme. The captodative effect of PLP is balanced by an enzyme active site that controls the deprotonation of both the pyridine nitrogen atom (N1) and the Schiff-base nitrogen atom (N2). Furthermore, electrostatic interactions between the terminal carboxylate and amino groups of the substrate and Arg297 and Glu81 impose substantial “strain” energy on the orientation of the cyclic intermediate to control its trajectory. In addition the “strain” energy, which appears to be sensitive to both the number of carbon atoms in the substrate/analogue and the position of the radical intermediates, may play a key role in controlling the transition of the enzyme from the closed to the open state. Our results provide new insights into several aspects of the radical mechanism in aminomutase catalysis and broaden our understanding of cofactor PLP-dependent reactions

Estudio cinetico de las reacciones de descomposicion e hidrolisis de N-Br-amino compuestos a-Descomposicion de N-Br-aminoacidos. b-Hidrolisis de N-Br-aminas

Available from Centro de Informacion y Documentacion Cientifica CINDOC. Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

Abordaje integral desde una perspectiva local de la violencia ejercida contra las mujeres. Fundamentos teóricos y propuestas para la intervención

Treball Final de Màster Universitari en Igualtat i Gènere en l'Àmbit Públic i Privat. Especialitat: Polítiques Públiques d'Igualtat. Codi: SAE030. Curs acadèmic 2013/201

The kinetics and mechanism of the acid-catalysed detritylation of nucleotides in non-aqueous solution

The kinetics and mechanism of the deprotection (detritylation) of 5-O-(4,4-dimethoxytrityl)-2-deoxythymidine nucleoside catalysed by dichloroacetic acid to give a 4,4-dimethoxytrityl carbocation have been studied in toluene, dichloromethane and acetonitrile. There is little or no effect of solvent polarity on the equilibrium and rate constants. Entropies of activation are highly negative -105 J K-1 mol-1 and similarly show little variation with solvent. Addition of small amounts of water to the reaction medium reduces the detritylation rate, presumably through its effect on the solution acidity. All observations are compatible with detritylation occurring through a concerted general acid-catalysed mechanism rather than a stepwise A1 process

Substituent Effects on the Thermodynamic Stability of Imines Formed from Glycine and Aromatic Aldehydes: Implications for the Catalytic Activity of Pyridoxal-5′-phosphate

Komunikacija predstavlja razmjenu ideja, misli i osjećaja između najmanje dvije osobe koje komuniciraju. U svakodnevnom poslovanju komunikacija predstavlja temelj svake tvrtke jer bez kolanja i dijeljenja informacija nemoguće je odvijanje poslovnih procesa. Komunikacija predstavlja vještinu koja ne mora biti urođena u čovjeka, već se može steći i kroz život odgovarajućim vježbama i tehnikama. Svaka osoba ima svoja prava koja se trebaju poštivati kako ne bi došlo do sukoba. Asertivnost svatko može različito definirati, ali bi se mogla predstaviti kao aktivnost zauzimanja neke osobe za sebe i svoja vlastita prava, predstavljanje svoga mišljenja i stava direktno, komunicirati otvoreno i nedvosmisleno te poštovati pravo druge osobe. U ovom završnom radu će se bolje prikazati komunikacija, njezina podjela i komunikacijski stilovi, a nakon toga će se pobliže opisati asertivnost i njezin značaj u poslovnoj komunikaciji. Zatim će se prikazati asertivne tehnike i njezini primjeri.Communication is the exchange of ideas, thoughts and feelings between two or more people. In everyday business, communication is the foundation of every business, because without the spin of information, business processes are impossible. Communication is a skill that does not have to be inborn, but can also be acquired through life through appropriate exercises and techniques. Every person has their rights to be respected so that there is no conflict. Assertiveness can be defined by everyone, but it can be presented as the activity of taking a person for himself and his own rights, presenting opinion and attitude directly, communicating openly and unambiguously and respecting the right of another person. In this final paper, communication, its division and communication styles will be better illustrated, and then it will be described more closely the assertiveness and its significance in business communication. Assertive techniques and examples thereof will then be presented