Disclosed is a new process and intermediates for preparing dipyrrolidine peptide compounds such as, for example, rapastinel. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.

The present disclosure relates to an in vitro method for enhancing engraftment of neurosensory precursor cell comprising the step of contacting an isolated neurosensory precursor cell prior to a transplantation in a subject in need thereof, with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate thereof:

##STR00001##

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I:

##STR00001##

where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.10, X, Y and n are as defined in the specification.

The present disclosure provides a more efficient route for preparing a crystalline form of a β-turn cyclic peptidomimetic compounds and salts thereof.

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I: ##STR00001##
where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.10, X, Y and n are as defined in the specification. The present disclosure provides a more efficient route for preparing a crystalline form of β-turn cyclic peptidomimetic compounds and salts thereof.

Methods for the synthesis of arginine-containing peptides are provided. The methods include a deprotection step that minimizes the transfer of by-products deriving from cleaved sulfonyl-5 based side chain protecting groups from arginine to amino acids carrying electron rich side chains.

The present disclosure relates to an in vitro method for enhancing engraftment of neurosensory precursor cell comprising the step of contacting an isolated neurosensory precursor cell prior to a transplantation in a subject in need thereof, with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate thereof: (I).

The invention provides a new oligopeptide linker intermediate and a preparation method thereof. The preparation method of the oligopeptide intermediate is easily carried out under mild reaction conditions, and since almost no side reactions occur in the reaction, the method produces a high-purity product with fewer impurities and easy to be purified, achieving unexpected technical effects.

The present disclosure provides compounds represented by Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.5a and R.sup.5b are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat a condition, disease, or disorder responsive to inhibition of the WDR5 interaction with its binding partners including, but not limited to, the WDR5-MLL protein-protein interaction.

##STR00001##

Certain embodiments of the invention provide a compound of formula (I):
R.sup.1C(O)WXYZN(R.sup.2).sub.2(I)
or a salt thereof, wherein R.sup.1, R.sup.2, W, X, Y and Z are as defined herein, as well as methods of use thereof.

The present invention discloses retro-inverso peptides and pharmaceutical composition containing them. The peptides of the invention prevent key events occurring during the metastatic process, i.e. invasion of the extracellular matrix, formation of a capillary network, and the entry into bloodstream. They are therefore useful in the treatment of diseases and conditions that are sustained by an increase of cell motility, cell invasion, and/or angiogenesis, such as tumors and chronic inflammation.