Peptide delayed absorption

The viscosity of the formulation can also influence the clearance of a drug. As reported in some papers, nasal sprays containing a viscous polymer such as methylcellu-lose or hydroxycellulose showed decreased clearance of the formulation from the nasal cavity, resulting in the delayed absorption of peptide drugs. 

Transient IR spectroscopy in the range of the amide I band is a direct tool to follow the structural dynamics of the peptide moiety. IR difference spectra on the bicyclic molecule bc-AMPB are plotted in Fig. 5. Shortly after excitation the absorption is dominated by a red shift. Such a red shift is expected for a strong vibrational excitation of the molecule. On the time-scale of a few picosecond this red shift decays to a large extent and is replaced by a dispersive feature of opposite sign at tD = 20 ps. At later delay times this feature changes details of its shape, it sharpens up and some substructure appears around 1680 cm 1. After 1.7 ns the shape is similar, but not completely identical to the difference spectrum recorded with stationary FTIR spectroscopy. This time dependence shows that the dominant structural change responsible for the IR difference spectrum occurs on the 20 ps time-scale and that minor structural changes continue until nanoseconds and even later times. 

Fig. 6. Left schematic potential energy curves explaining the absorption transients seen in the newly formed trans-absorption bands. The strain between the peptide part and the azobenzene chromophore delays the transition to the relaxed ground state and causes the blue-shift observed as a function of time. Right View of the two phases of peptide motion occurring after the initial isomerzation of the azobenzene chromophore.

A novel pump-damp-probe method (PDPM), which allows the characterization of solvation dynamics of a fluorescence probe not only in excited but also in the ground states has been recently developed (Changenet-Barret, 2000 and references therein). In PDPM, a pump produces a nonequilibrium population of the probe excited, which, after media relaxation, is simulated back to the ground states. The solvent relaxation of the nonequlibrium ground state is probed by monitoring with absorption technique. The inramolecular protein dynamics in a solvent-inaccessible region of calmodulin labeled with coumarin 343 peptide was examined by PDPM. In the pump-dump-probe experiments, part of a series of laser output pulses was frequency-doubled and softer beams were used as the probe. The delay of the probe with respect to the pump was fixed at 500 ps. 

Fig. 4. (a) Absorption change recorded for c-APB at certain delay times to- These spectra show the spectral shift of the newly formed trans bands on the 10 - 100 ps time scale, (b) excitation energy corresponding to the peak absorption of the 350 nm band plotted as a function of time (filled circles) and time dependence of the energy within the peptide determined by MD-simulations (points). 

Chylomicrons deserve particular attention in TD since their protein moiety normally contains peptides identical with those of HDL (Rodbell and Fred-RiCKSON 1959 Scanu and Page 1959 Fredrickson 1965). Fat absorption pro-cedes normally in TD, and TD-chylomicrons behave like normal chylomicrons upon ultracentrifugation and phase contrast microscopy. They are dissimilar from the normal particles in that their cholesterol content is only about one quarter that of normal chylomicrons, while phospholipid concentration is normal (see table 4). A slight delay in chylomicron removal was found in some patients (Fredrickson 1966). 

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