Electronic substituent effect on the conformation of a phenylalanine-incorporated cyclic peptide.

The Phe-incorporated cyclic peptide [cyclo(-Phe1-oxazoline2-d-Val3-thiazole4-Ile5-oxazoline6-d-Val7-thiazole8-)] is in a conformational equilibrium between square and folded forms in solution. In the folded form, a CH⋯π interaction between the Phe1 aromatic ring and the Oxz2 methyl group is observed. We endeavored to control the local conformation and thus modulate the CH⋯π interaction and flexibility of the Phe1 side chain by controlling the electronic substituent effects at the 4-position of the aromatic ring of the Phe1 residue. The effect of the 4-substituent on the global conformation was indicated by the linear relationship between the conformational free energies (ΔGo) determined through NMR-based quantification and the Hammett constants (σ). Electron-donating substituents, which had relatively strong CH⋯π interactions, promoted peptide folding by restraining the loss in entropy. Local control by the 4-substituent effects suggested that the Phe side chain exerts an entropic influence on the folding of these cyclic peptides.

Distribution of 5HT receptors during the regeneration process after spinal cord transection in goldfish.

Spinal cord injury in teleosts leads to a fibrous scar, but axons sometimes spontaneously regenerate beyond the scar. In goldfish, regenerating axons enter the scar through tubular structures and enlargement of the tubular diameter is proportional to the increase in the number of regenerating axons. During the regeneration process, mast cells containing 5-hydroxytryptamine (5HT) are recruited to the injury site, and 5HT neurons are newly generated. Here, we investigated the distribution of 5HT receptors during this process to determine their role in remodeling the fibrous scar and tubular structures. At 2 weeks after spinal cord transection (SCT) in goldfish, expression of the 5HT2A and 5HT2C receptor subtypes was observed in the ependymo-radial glial cells lining the central canal of the spinal cord. 5HT2A was expressed at the luminal surface, suggesting that it is receptive to 5HT in the cerebrospinal fluid. 5HT2C, on the other hand, was expressed around the nuclei and in the radial processes protruding from the basal surface, suggesting that it is receptive to 5HT released from nearby nerve endings. 5HT2C was also expressed in the fibrous scar where mast cells containing 5HT were abundant. 5HT1B expression was coincident with the basement membrane bordering the fibrous scar and the surrounding nervous tissue, and with the basement membrane of the tubular structure through which axons pass during regeneration. Our findings suggest that multiple 5HT receptors are involved in remodeling the injured site during the regenerative process following SCT. Ependymo-radial glial cells expressing 5HT2A and 5HT2C are involved in neurogenesis and gliogenesis, which might contribute to remodeling the fibrous scar in coordination with 5HT-containing mast cells. Coincident expression of 5HT1B with the basement membrane might be involved in remodeling the tubular structures, thereby promoting axonal regeneration.