Stereoisomer peptides, their polymer conjugates, their encapsulation into nanoparticles, and uses thereof for the treatment of diseases caused by abnormal angiogenesis

A ligand-targeted multi-stereoisomer peptide-polymer conjugate compound comprising the formula:

• [sP]n-(L)-Pol-sPL, or a pharmaceutical composition thereof, wherein:
• [sP]n is a group of 2 to 4 different stereoisomer peptides,
• wherein the 2 to 4 different stereoisomer peptides are selected from within
• 1) SEQ ID NOs:
• 7, 8, 9 and 113;
• 2) SEQ ID NOs:
• 7, 12, 17 and 27;
• 3) SEQ ID NOs:
• 7, 11, 12 and 17;
• 4) SEQ ID NOs:
• 7, 109, 110 and 124;
• 5) SEQ ID NOs:
• 45, 46, 48, and 70;
• 6) SEQ ID NOs:
• 48, 99, 102 and 105;
• 7) SEQ ID NOs:
• 106, 108, 113 and 128;
• 8) SEQ ID NOs:
• 104, 116, 117, and 133;
• 9) SEQ ID NOs:
• 107, 116, 117, and 136;
• 10) SEQ ID NOs:
• 119, 122, 123 and 155;
• 11) SEQ ID NOs:
• 138, 141, 142 and 143;
• 12) SEQ ID NOs:
• 137, 139, 142 and 143;
• or
• 13) SEQ ID NOs:
• 144, 145, 146 and 147,
• wherein any of the amino acids in each of the stereoisomer peptides can be in D or L form and, optionally, where D-amino acid peptides are in inverso or retro-inverso configuration,
• wherein each of the 2 to 4 different stereoisomer peptides in said group is connected to Pol via (L),
• L is a non-cleavable linker comprising
• Gly-Gly or Lys-Lys, or a cleavable linker comprising
• SEQ ID NO:
• 315 or SEQ ID NO:
• 316,
• Pol is poly lactic-co-glycolic acid (PLGA) or a derivative thereof,
• sPL is a stereoisomer peptide ligand comprising SEQ ID NO:
• 8, 10, 43, 85, 103, or 154,
• and wherein said stereoisomer peptides each target the functional domain of a different specific target protein involved in diseases caused by abnormal angiogenesis to inhibit, antagonize, bind, block, disrupt, interact or suppress, each simultaneously and independently, and positively or negatively said target protein, wherein said target protein is selected from VEGF, VEGFR-1, VEGFR-2, EGFR, PDGFR, FGF, NgR, HSP90, HSP70, HSP72, HSC70, av33, av35, a531, NRP-1, neuroepithelin, proepithelin, p53, MMP-1, 3, and 8, collagen type IV and type XVIII, tumnstatin, endostatin, TSP-1, p13K, TAK-1, akt, STAT3, MAPK, a-synuclein, 0-amyloid, mTOR, GSK3b, myelin, tau, PolyQ peptide, PRNP, BDAI, CCL5, CCR3, CXCR6, amino peptidase-P, annexin Al, gp120, gp41, p24, tat, protease, integrase, reverse transcriptase, Vif, PfCDPK1, UIS3, DHFR-TS, or Acps.