Loop sequences

In contrast to the work described above, which examined the length of G-quadruplex loops, Todd and Neidle focussed primarily on the sequence of the loops. It is known that the sequences of the loops of G-quadruplex can affect their structure and stability.They firstly showed that there are many potential loop sequences found in PQS (10,551 unique loops sequences), although this does not cover the entire sequence space available there are 12,289 possible sequences, of which only 85% are actually found. 

They examined a variety of properties, focusing on two principle ones - the frequency of various sequences, and the degree to which individual sequences are found in one loop rather than the others. 

The most frequent loops are shown in Table 5 below. As described earlier, these results show that single-base loops are very common, and that in general. 

---

Kaushik N., Pandey V. N. PNA targeting the PBS and A-loop sequences of HIV-1 genome destabilizes packaged tRNA3(Lys) in the virions and inhibits HIV-1 replication. Virology 2002 ... 

The engineering of zinc-binding sites in a-helical peptides, where metal binding stabilizes protein tertiary structure, has been reported by Handel and DeGrado (1990). In these experiments zinc-binding sites are incorporated into a dimeric helix-loop—helix peptide (H3 2) and a protein composed of four helices connected by three short loop sequences (H3 4). a model of one subunit of the H3 2 dimer is found in Fig. 47. In addition to metal complexation by two histidine residues at positions n and n+4 of one a helix, the metal is coordinated by a third histidine residue of an adjacent a helix. The composition of the zinc coordination polyhedron is like that of carbonic anhydrase (i.e., Hiss), and spectroscopic results suggest that all three histidine residues are involved in zinc complexation. This work sets an important foundation... 

Several nucleotides that were more effective inhibitors than the originally tested AZT nucleotides were identified [71]. For example, the L-enantiomers of 5-fluoro-2, 3 -dideoxycytidine monophosphate and triphosphate inhibit 3 processing and strand transfer with IC50 values of 40 pM. A structure-function study on GT-containing oligonucleotides showed that both the number of quartets formed and the loop sequences between the quartets are important for activity, and that inhibitors of this type may function by interacting with the N-terminus of integrase [72]. 

Table II. D-Loop sequencing primers and their annealing temperatures. ... 

Scheme 28 Strategies A-D for the Fixation of Peptide Loop Sequences (L,) to Topological Templates (Tj)[381 A (A )...

Scheme 30 The Immobilization of a Regioselectively Addressable Decameric Template Allows for the Sequential Attachment of Two-Loop Sequences in a Defined Orientation 5153 ...

Fig. 17. An incremental approach to the design of a four-helix bundle protein (Ho and DeGrado, 1987). (a) The sequence of a peptide is first optimized for forming a very stable tetramer of a helices. The stability of the tetramer can be assessed from the dissociation constant for the cooperative monomer-to-tetramer equilibrium, (b) Two optimized helical sequences are then connected in a head-to-tail manner by a single loop. The loop sequence can be optimized by evaluating a series of alternate designs, (c) Finally, the entire four-helix bundle structure can be constructed from four optimized helices and three optimized loops.

Honsho, M., and Fujiki, Y (2001). Topogenesis of peroxisomal membrane protein requires a short, positively charged intervening-loop sequence and flanking hydrophobic segments—study using human membrane protein PMP34. /. Biol. Chem. 276, 9375-9382. 

---