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Carbon-13 spin-lattice relaxation times of the tripeptide methyl ester Boc-Gly-Pro-Pro-OMe and its polymer-bound analogues are reported. Line widths of the signals of -carbon atoms of Pro(2) and Pro(3) are also measured and an interpretation of the line broadening is presented. As polymeric macromolecules the following supports were employed: insoluble cross-linked polystyrene (PS), soluble poly(oxyethylene) (POE), and the graft copolymer poly(oxyethylene)-polystyrene-divinylbenzene (POE-PS). The molecular motions of the peptide moieties were determined by analysis of the relaxation time Tv The peptide methyl ester was synthesized classically and after saponification of the ester group it was coupled to the polymers according to known procedures. In the present studies for the measurements of the Tj values only the signals of the trans forms of the X-Pro sequence have been considered. The investigations revealed that the Tt values and hence the mobility of the C atoms of the peptide esters decrease in the sequence methyl ester > POE ester > POE-PS ester > PS ester.

A library system was developed for the discovery of bioactive peptides. Library synthesis and peptide sequencing was performed on a solid support while the screening for bioactivity was done with peptides in solution. The peptides were synthesized by split and mix, one-bead-one-peptide library synthesis, using a Tentagel S-NH2 solid support with a loading of approximately 100 pmol/bead. The major part of the peptide was connected to the support by a single acid-labile linker and a minor part of the peptide was acid-stabile attached to the polymer. The percentage of acid-stabile attached peptides could easily be controlled during modification of the amino functionalities of the resin at the start of the process. The cleavage rate of the acid-labile attached peptide from the resin depends on the composition of the cleavage mixture. When cleavage conditions were carefully controlled, a three-step partial cleavage protocol allowed for convergent bioactivity screening on peptide libraries using only one type of acid-labile linker. The partial cleavage and convergent screening procedure was repeated three times, after which the bead containing the bioactive peptide was sequenced. As such a bead still contained acid-stabile attached peptide, the Edman sequencing was straightforward and repetitive yields were excellent because the immobilized peptide was not washed out.

The preparation of a dendritic graft polymer by a very efficient synthesis of polyglycerol directly on a polystyrene resin is presented. This one-step process can be performed on a multigram scale to provide a chemically stable polymeric support. The resulting hybrid polymers were fully characterized by diverse analytical methods (NMR, IR, ESEM, UV detection of cleaved protecting groups, and mass-spectrometric methods). They combine a high loading capacity (up to 4.3 mmol g(-1)) with good swelling properties in a wide range of solvents (including water), which is the major drawback for many existing solid phase supports. In comparison to the widely employed PEGylated resins, these hybrid materials offer a 10-fold higher loading capacity. Their suitability as supports for organic synthesis and for the immobilization of reagents has been demonstrated. These materials also swell in water, and consequently, it should be possible to use these new hybrid materials for synthesis in protic solvents.