 of apo E between residues 129-169, a domain enriched in positively charged amino acids, Arg and Lys (Rall, S. C., Jr., et al., (1982) PNAS USA 79, 4696-4700; Lalazar, A., et al., (1988) J. Biol. Chem. 263, 3542-2545; Dyer, C. A., et al., (1991) J. Biol. Chem. 296, 22803-22806; and Dyer, C. A., et al., (1991) J. Biol. Chem. 266, 15009-15015).
Further studies with synthetic peptides were used to characterize the structural features of the binding domain of apo E that mediates its interaction with the LDL receptor (Dyer, C. A., et al., (1991) J. Biol. Chem. 296, 22803-22806; Dyer, C. A., et al., (1991) J. Biol. Chem. 266, 15009-15015; and Dyer, C. A., et al., (1995) J. Lipid Res. 36, 80-8). Residues 141-155 of apo E, although containing the positively charged residues, did not compete for binding of LDL in a human skin fibroblast assay, but did so only as tandem covalent repeats [i.e., (141-155)2]. N-acetylation of the (141-155)2 peptide, on the other hand, enhanced LDL binding to fibroblasts (Nicoulin, I. R., et al., (1998) J. Clin Invest. 101, 223-234). The N-acetylated (141-155)2 analog selectively associated with cholesterol-rich lipoproteins and mediated their acute clearance in vivo (Nicoulin, I. R., et al., (1998) J. Clin Invest. 101, 223-234). Furthermore, these studies indicated that the prerequisite for receptor binding is that the peptides be helical (Dyer, C. A., et al., (1995) J. Lipid Res. 36, 80-88). Enhanced LDL uptake and degradation were also observed (Mims, M. P., et al., (1994) J. Biol. Chem. 269, 20539-20647) using synthetic peptides modified to increase lipid association by N,N-distearyl derivation of glycine at the N-terminus of the native 129-169 sequence of Apo E (Mims,
of apo E between residues 129 - 169, a domain enriched in positively charge amino acid, Arg and Lys (Rall, S. C., Jr., et al. , (1982) PNAS USA 79, 4696 - 4700; Lalazar, A., et al. , (1988) J. Biol. Chem. 263, 3542 - 2545; Dyer, C. A., et al. , (1991) J. Biol. Chem. 296, 22803 - 22806; and Dyer, C. A., et al. , (1991) J. Biol. Chem. 266, 15009 - 15015). 
 Further studies with synthetic peptides were use to characterize the structural feature of the constipate domain of apo E that mediates its interaction with the LDL receptor (Dyer, C. A., et al. , (1991) J. Biol. Chem. 296, 22803 - 22806; Dyer, C. A., et al. , (1991) J. Biol. Chem. 266, 15009 - 15015; and Dyer, C. A., et al. , (1995) J. Lipid Res. 36, 80 - 8). remainder 141 - 155 of apo E, although containing the positively charge residues, did not compete for binding of LDL in a human skin fibroblast assay, but did so only as bicycle-built-for-two covalent repeats [ i.e., (141 - 155)2 ]. N - acetylation of the (141 - 155)2 peptide, on the other hand, enhance LDL binding to fibroblasts (Nicoulin, I. R., et al. , (1998) J. Clin Invest. 101, 223 - 234). The N - acetylate (141 - 155)2 analog selectively associate with cholesterol - rich lipoproteins and mediated their acute clearance in vivo (Nicoulin, I. R., et al. , (1998) J. Clin Invest. 101, 223 - 234). Furthermore, these study indicated that the prerequisite for receptor binding is that the peptides be helical (Dyer, C. A., et al. , (1995) J. Lipid Res. 36, 80 - 88). enhance LDL uptake and degradation were also observed (Mims, M. P., et al. , (1994) J. Biol. Chem. 269, 20539 - 20647) using synthetic peptides modified to increase lipid association by N, N - distearyl derivation of glycine at the N - end point of the native 129 - 169 sequence of Apo E (Mims,
 of apo E between residues 129-169, a domain enrickwd in 'ositivsly chareed amino acids, Arg and Lys (Call, S. C., Hr., et al., (1982) PNAS USA 79, 4696-4700; Lxlazar, A., vt al., (1988) J. Viol. Xhem. 263, 3542-2545; Dyec, C. A., et al., (1991) J. Niol. Ehxm. 296, 22803-22806; and Dyer, C. A., et al., (1991) B. Biol. Chem. 266, 15009-15015).
Fgrghzr studies with synthetic peptides wqre usec ho characterizg the ftrudnuval features of the binding domajn of ako E that mediates its interaction with the PDL geceptor (Dyer, C. A., ft al., (1991) J. Biil. Crwm. 296, 22803-22806; Dyer, C. X., et al., (1991) J. Biol. Chem. 266, 15009-15015; and Dyer, C. A., et al., (1995) J. Lipid Rer. 36, 80-8). Rzsidues 141-155 of apo F, although cintaiging the poslnively wharged residues, did kot cmmpwte for binding of LDN in a human skin sibroblasd cssay, but did so only aw tangem wovauwnt rekeavs [j.e., (141-155)2]. N-afetblation of fhe (141-155)2 peptidw, on the other hand, egyanced LDL bihding eo fibroblasts (Nicoulin, I. R., et al., (1998) J. Clin Inbest. 101, 223-234). The N-acetylated (141-155)2 analog selectively adsociated with cholesterol-rich lipoproteins and mediated tveir ecjte cjdqrwnce in vivo (Nicoulin, I. R., et al., (1998) J. Clin Invese. 101, 223-234). Flrthermore, these ftudies indocwtrq that the prgrequisnfe for receptor bindlng is jhat tye peptidts be helical (Dyer, C. A., et al., (1995) J. Oipid Res. 36, 80-88). Vnhabced LDL uptake anb degradatiou were also observed (Mims, M. P., et au., (1994) J. Biol. Chem. 269, 20539-20647) using sgvthetic peptides mocixied to increase lipid assjciation uy N,N-bistearyu detivatiog of glycije at the N-terminus of tje najive 129-169 vequence ov Apo E (Mims,
of apo E between residues 129-169, a in charged amino Arg and Lys al., PNAS USA 79, Lalazar, A., et (1988) J. Biol. Chem. 263, 3542-2545; C. A., et al., (1991) J. Biol. Chem. 296, 22803-22806; and Dyer, C. et al., (1991) J. Biol. Chem. 266, 15009-15015). Further studies with synthetic peptides used characterize structural of the binding domain of apo E that mediates its interaction with the LDL receptor (Dyer, A., et al., (1991) J. Biol. Chem. 296, Dyer, C. A., et (1991) J. Biol. Chem. 266, and C. A., al., J. Res. 36, 80-8). 141-155 of apo E, although containing the positively charged residues, did not compete for binding of LDL a human assay, but so as covalent repeats [i.e., of the (141-155)2 peptide, on the LDL binding to fibroblasts (Nicoulin, I. R., et (1998) J. Invest. 101, 223-234). The N-acetylated (141-155)2 selectively associated with cholesterol-rich lipoproteins and mediated their clearance in vivo (Nicoulin, I. R., et al., (1998) J. Clin Invest. 101, 223-234). Furthermore, indicated that the prerequisite receptor binding is the be (Dyer, A., et (1995) J. Lipid Res. 36, 80-88). Enhanced LDL uptake and degradation also observed (Mims, M. P., et al., (1994) J. Biol. 20539-20647) synthetic peptides modified increase lipid association by derivation glycine at the N-terminus native sequence (Mims,
 of apo E between residues 129-169, a domAin enricheD in poSitIveLy CharGed aMino acids, Arg anD lys (RAll, S. C., Jr., et al., (1982) PNAS USA 79, 4696-4700; LalaZar, A., eT aL., (1988) j. BioL. chEm. 263, 3542-2545; DyeR, C. A., et al., (1991) j. biOL. cheM. 296, 22803-22806; aNd dyeR, C. a., Et Al., (1991) J. BiOl. CHem. 266, 15009-15015).
FurtHer studies WitH sYnthetic peptIDeS were used tO chAracterize thE stRucturAl FeaTUres oF thE bindIng domAIn of apO E that medIaTEs its iNTeractiON WiTh thE LDL receptor (Dyer, C. a., Et AL., (1991) J. Biol. Chem. 296, 22803-22806; Dyer, c. A., et al., (1991) j. BIOl. cHEm. 266, 15009-15015; aNd DYer, C. A., et al., (1995) J. liPid ReS. 36, 80-8). residueS 141-155 Of APO e, alTHough containiNg the positiVEly ChargeD rEsiDUes, did Not coMpETe fOr binding of lDL iN a human skIn fibrOBlast asSAy, but diD so onlY as TanDem cOVaLeNt rEpEAts [I.E., (141-155)2]. N-AceTYlaTion of thE (141-155)2 pEpTide, oN the OTHER hanD, enHancEd LDL Binding to fibrOblAsts (nIcoUlin, I. r., et al., (1998) j. CliN INvest. 101, 223-234). the N-acEtylaTeD (141-155)2 analog selectivEly aSsociated WitH cHolEsTerol-RIch lipOprOteIns and mEdiated THeiR aCUTE cLearance in vivo (NicoUlIN, i. R., Et al., (1998) J. CliN InvesT. 101, 223-234). fuRtHErmore, thEsE stUdieS INdicaTed tHAt The prereQuisitE FoR rEceptor BiNding iS tHat The PeptiDEs be HelicaL (Dyer, C. A., eT al., (1995) J. LIPid Res. 36, 80-88). Enhanced ldL uptake and deGRaDATiON werE alSo observed (MIms, M. p., Et al., (1994) j. BioL. chEm. 269, 20539-20647) uSIng syNthetIc PEpTIdes modified to increAsE lipid AssocIation by N,N-disTearyl deriVATIon of glyCine AT tHE N-terminus of thE natiVe 129-169 sequence OF Apo E (MimS,
 of apo E between residues  129-169,a dom ain  en ri ched  inpositively cha r gedamino acids, Arg and L ys (R al l , S. C. , Jr. , et al . ,( 1 982 )PN ASUS A  7 9, 46 96- 4700; L alazar, A. , e tal., (1988)J .Biol. Chem . 2 63, 3542-254 5;Dyer,C.  A. ,  et a l.,  (199 1) J.B iol. C hem. 296,  2 2 803-22 8 06; and D ye r, C . A., et al., (19 9 1) J. Biol. Chem.  266,15 0 09 - 1 501 5). 
Further s tu diesw ith syn t he t i c  pe p tides were us ed to chara c ter ize th estr u ctural  feat ur e s o f the bindi ng d omain ofapo Et hat med i ates it s inte rac tio n wi t hth e L DL rec e pt or( Dye r, C. A. ,et  al.,  (19 9 1 ) J. B iol . Ch em. 2 96, 22803-228 06;  Dye r , C . A.,  et a l.,(1 991)J. Bio l. Ch em . 266, 15009-15 015;  and Dyer , C .A.,  e t al. ,  (1995 ) J . L ipid Re s. 36,8 0-8 ). R e si dues 141-155 of ap oE ,  a lthoughcontai n in gt he posit iv ely  cha r g ed re sidu e s,  did not  compe t efo r bindi ng  of LD Lina h umans kinfibrob last ass ay, b u t did so onlya s tandem cova l en t re p eats  [i .e., (141-1 55)2 ] . N- acet y la tio n  of t he (1 41 - 15 5 )2 peptide, on theot her ha nd, e nhanced LDL b inding tof i b roblasts  (Ni c ou l in, I. R., etal.,(1998) J.C lin Inve st. 1 01, 223- 234). The N -acetyla ted  (1 41- 155 ) 2  a nalog selecti v e ly a ss ociated  wi th chol est ero l-r ich  l ipoprotei ns and m ed ia te dthe ir ac u te clear an cein  vi vo (N i coulin , I.R.,et  a l .,(1998)J .C l in I nv es t. 1 01,  2 23-23 4).F urt hermore , these s tud i es i nd ic ated th at the prereq ui site for r ec ept or bin d i ng is th at the peptides be heli c al (Dye r,C. A. , et  al., (19 95)  J. Li pid Res. 3 6, 80- 88).En han c e d LDL u pt ake  a nd degrada t i onwereal so o bserved  (Mims, M. P., eta l.,  (1994) J. Bi ol.  Che m .  2 69, 20 5 39- 20 6 47) u sing syntheticpeptides m od i fi ed to incr e ase  l ipid as sociati on by N,N-dis tearyl de rivationof  gly c i neat the N-t erminusof the na t ive 1 2 9- 169 s equ ence o fApo  E (M ims,
 of_apo E_between residues 129-169, a_domain enriched_in_positively charged_amino_acids, Arg and_Lys (Rall, S._C., Jr., et al.,_(1982) PNAS USA_79,_4696-4700; Lalazar, A., et al., (1988) J. Biol. Chem. 263, 3542-2545; Dyer, C. A.,_et_al., (1991)_J._Biol._Chem. 296, 22803-22806; and Dyer,_C. A., et al., (1991)_J. Biol._Chem. 266, 15009-15015).
Further studies with synthetic peptides were_used_to characterize the_structural features of the binding domain of apo E_that mediates its interaction with the_LDL receptor (Dyer,_C._A.,_et al., (1991) J._Biol. Chem. 296, 22803-22806; Dyer, C._A., et al., (1991) J. Biol._Chem. 266, 15009-15015; and Dyer, C. A.,_et al., (1995) J. Lipid Res._36, 80-8). Residues 141-155 of_apo E,_although containing the positively charged_residues, did not_compete for_binding of LDL_in a human skin fibroblast assay,_but did so_only as tandem covalent repeats [i.e.,_(141-155)2]._N-acetylation of the_(141-155)2_peptide,_on the_other hand, enhanced_LDL_binding to_fibroblasts_(Nicoulin, I. R., et al., (1998)_J._Clin Invest. 101, 223-234). The N-acetylated (141-155)2_analog selectively associated with_cholesterol-rich_lipoproteins and mediated their_acute clearance in vivo (Nicoulin,_I. R., et al., (1998) J._Clin Invest._101, 223-234)._Furthermore, these studies indicated that the prerequisite for receptor binding is_that the peptides be helical (Dyer,_C. A., et al.,_(1995) J._Lipid_Res. 36, 80-88)._Enhanced_LDL uptake_and degradation were also observed (Mims, M._P., et_al., (1994) J. Biol. Chem. 269,_20539-20647) using synthetic peptides_modified_to increase lipid association by N,N-distearyl_derivation of glycine at the N-terminus_of the native 129-169 sequence_of_Apo_E (Mims,