الفهرس 
Acknowledgement
ChemistryOnly 14 pages are availabe for public view
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Abstract
The submitted dissection is prefaced by a comprehensive literature survey so as to cast some light on the human immunodeficiency virus (HIV), its life cycle, the role of protease enzyme. Moreover the thesis included a literature survey on different HIV-1 PR inhibitors and their design which were based on the classical HIV PR substrates, transition-stale analogues, or structure-based non peptide inhibitors.
The present investigation is concerned with design, synthesis and SAR requirements for HIV-I protease inhibitor)’ activity of a new series of inhibitors containing allophenylnorstatine (Apns) a transition-state containing residue.
Keeping in mind KN1-279 (iQOA-Val-Apns-Thz-NHBu1) as a lead molecule, the designed derivatives include two series of compounds.
• Tripeptides, systematic replacement at the sites from P2 through Apns (PI ) to P3 was performed in order to study each site requirements.
• Dipeplides. stud) the N-terminal (P2) replacement by different aromatic and aliphatic carboxylic acids.
The transition stale containing element. Apns. was prepared using the most convenient method.
The strategy of preparation of targeted peptide inhibitor was based on solution peptide synthesis protocol starling from the C-terminal residue (PI’). The synthesis was started’ by coupling of the N-(Boc) C-activated amino acid or PI’ with the free amino group of the P2’ residue. Unmasking the ammo group of the coupled product was conducted before the coupling with the text amino acid. Boc- Apns. This step was repeated with the next appropriate amino acid to be incorporated until finishing the synthesis of the required compound. The final compounds were purified by preparative HPLC and obtained as a lypholized powder.
Some compounds were derived from the finally built tripeptides through chemical modification e.g oxidation of Apns in the tripeptides to a- keto amides (18-21).