Biomolecule labeling

Jaouen, G. In Bioorganometallics Biomolecules, Labeling, Medicine Wdey-VCH Weinheim, 2006. 

Relaxation in Coupled Spin Systems. - The ability to transfer coherences between different nuclei in homo- and heteronuclear spin systems is one of the cornerstones of NMR. The transfer of polarization from I = (1/2) to enhance the signal of low-gyromagnetic ratio S = (1/2) nuclei has become routine. In solution state the majority of these methods employ free-precession type techniques such as INEPT where polarization transfer from one spin to another is mediated via the scalar coupling. The majority of these techniques are designed for spin-half systems and have shown particular utility in the study of structure and dynamics of biomolecules labeled with C and N. The use of INEPT for achieving polarization transfer in systems of scalar coupled quadrupolar nuclei has also been investigated. ... 

The carbonyl functionality is a prevalent structure in many biomolecules. Labeling in this position can be achieved by reaction with [ phosgene (Roeda et al. 1978 Roeda and Westera 1981 Nishijima et al. 2002, see also Fig. 41.14) and acyl chlorides such as acetyl- (Luthra et al. 1990), cyclohexanecarbonyl-, (McCarron et al. 1996), and furoyl chloride (Ehrin et al. 1988). 

Keywords Bioorthogonal reactions Click chemistry Biomolecule labeling 1,3-dipolar cycloaddition Diels-Alder reaction... 

Fig. 3 Examples of 1,3-dipoles used for biomolecule labeling. The resonance structures are shown in the sextet (on the and the octet formula (on the right), respectively...

Strain-promoted alkyne-nitrone cycloaddition (SPANC) is another example of a 1,3-dipolar cycloaddition that has been applied for biomolecule labeling. The reactivity of nitrones with strained alkynes can be finely tuned by varying the substitution pattern [46-48]. Various cyclic nitrones were found to react with superior kinetics when compared to their acyclic counterparts and were successfully... 

The DA reaction is controlled by the energy gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the reactants (Fig. 13). The rate of the reaction can be significantly enhanced by using Lewis acid catalysis. An attractive feature of the DA reaction to biomolecule labeling is the observed rate enhancement in polar solvents, including water [71, 72]. The DA reaction fulfills the criteria of click reaction, and therefore plays a key role in modern bioorthogonal chemistry. 

Biomolecules labeled with (aUcyne)[Co2(CO)g] entities are among the most widely studied molecules in bioorganometallic chemistry, thanks to their ease of preparation and reasonable stabiUty [96], It is thus no surprise that the Uterature provides examples of peptides [97, 98], proteins [99], therapeutic drugs [100], abortifacient medications such as RU486, 35 [101], corticoids and androgens [102], methotrexate 37 [103], the mycotoxin zearalenone 36 [104, 105], estrogens [106-110] and pesticides [111] modified by this entity (Scheme 3.15). 

Jaouen, G. Beck, W. McGlinchey, M. J. In Bioorganometallics Biomolecules, Labeling, Medicine, Jaouen, G., Ed. Wiley-VCH Verlag GmBH Weinheim, 2006 p 1. 

In a biomolecule, labelled with two Gd(m) labels and two nitroxide radicals, the measurement of Gd(iii)-nitroxide distances would in general produce an overlap of four distance distributions from all possible combinations of Gd(iii) and nitroxide labelling sites. Such measurements could provide important qualitative information, but their quantitative use might be limited. For instance the nitroxide-nitroxide and Gd(in)-Gd(iii) distances could be monitored in two different types of biomolecules and the distance changes upon complex formation could be further supported by the independent proof of the presence of the complex from Gd(iii)-nitroxide DEER. 

---