Abstract: [Abstract] Objective To compare the biodistribution difference of peptide nanofibers which were self-assembled by peptide composed of L- or D-amino acids, respectively. And provide guidance for the in vivo applications of peptide nanofibers. Methods The Nap-GFFYGRGD (L-peptide) and Nap-GDFDFDYGRGD (D-peptide, F and Y were D-configuration) were synthesized with solid phase peptide synthesis (SPPS). The structure of the two peptides was identified by nuclear magnetic resonance spectroscopy (1H NMR) and high-resolution mass spectrometry (HR-MS). The two peptides could self-assemble into nanofibers during the cooling process after being boiled and the morphology of the nanofibers was observed with transmission electron microscope (TEM). The peptides were radiolabled with iodine-125 and self-assembled into nanofibers, then administrated into BALB/c mice via tail vein. The blood was collected and then the mice were sacrificed at 1, 3, 6 and 12 hours. The main organs (heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, muscle and brain) were isolated and weighed. The radioactivity of organs was detected with a gamma counter. Results The two peptides could self-assemble into nanofibers with diameter of 10-20 nanometers. The diameter and morphology of the two naofibers had no statistically significant difference. Biodistribution of the two nanofibers had statistically significant difference. The concentration of L-fiber in blood at one hour after injection was 5.9±0.30 %ID/g and maintained at a stable level during six hours after injection. While the conterpart of D-fiber was 8.17±0.32 %ID/g and then cleared rapidly from the blood. The L-fiber mainly accumulated in stomach while the D-fiber mainly accumulated in liver. Conculsion The configuration of amino acids (D/L) could affect the biodistribution of peptide nanofibers dramatically, this results may provide guidance for the medical applications of peptide nanofibers.

Key words: peptides, amino acid sequence, isotope labeling, tissue distribution, peptide nanofiber